| 1. |
- Abedi-Ardekani, B, et al.
(författare)
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Morphological findings in frozen non-neoplastic kidney tissues of patients with kidney cancer from large-scale multicentric studies on renal cancer
- 2021
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Ingår i: Virchows Archiv : an international journal of pathology. - : Springer Science and Business Media LLC. - 1432-2307. ; 478:6, s. 1099-1107
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Tidskriftsartikel (refereegranskat)abstract
- There are unexplained geographical variations in the incidence of kidney cancer with the high rates reported in Baltic countries, as well as eastern and central Europe. Having access to a large and well-annotated collection of “tumor/non-tumor” pairs of kidney cancer patients from the Czech Republic, Romania, Serbia, UK, and Russia, we aimed to analyze the morphology of non-neoplastic renal tissue in nephrectomy specimens. By applying digital pathology, we performed a microscopic examination of 1012 frozen non-neoplastic kidney tissues from patients with renal cell carcinoma. Four components of renal parenchyma were evaluated and scored for the intensity of interstitial inflammation and fibrosis, tubular atrophy, glomerulosclerosis, and arterial wall thickening, globally called chronic renal parenchymal changes. Moderate or severe changes were observed in 54 (5.3%) of patients with predominance of occurrence in Romania (OR = 2.67, CI 1.07–6.67) and Serbia (OR = 4.37, CI 1.20–15.96) in reference to those from Russia. Further adjustment for comorbidities, tumor characteristics, and stage did not change risk estimates. In multinomial regression model, relative probability of non-glomerular changes was 5.22 times higher for Romania and Serbia compared to Russia. Our findings show that the frequency of chronic renal parenchymal changes, with the predominance of chronic interstitial nephritis pattern, in kidney cancer patients varies by country, significantly more frequent in countries located in central and southeastern Europe where the incidence of kidney cancer has been reported to be moderate to high. The observed association between these pathological features and living in certain geographic areas requires a larger population-based study to confirm this association on a large scale.
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| 2. |
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| 3. |
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| 4. |
- Alm, P., et al.
(författare)
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Immunoglobulin-A producing probably primary lymphoma of the breast
- 1983
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Ingår i: Virchows Archiv. - 1432-2307. ; 399:3, s. 355-360
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Tidskriftsartikel (refereegranskat)abstract
- A breast tumour from a 65-year old woman was found to be a primary non-Hodgkin lymphoma, a very rare primary malignancy in this location. The lymphoma was of a diffuse histiocytic type according to the classification of Rappaport, or polymorphic immunocytoma according to the Kiel classification. Immunohistochemistry, not previously reported for breast lymphomas, revealed the production of IgA. In the serum this appeared as an IgA M-component which was greatly reduced after tumour removal. Immunological properties of primary breast lymphomas are reviewed, we suggest further extended studies with the immunohistochemical use of marker substances for the evaluation of prognosis. © 1983 Springer-Verlag.
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| 8. |
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| 9. |
- Almangush, A, et al.
(författare)
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Stromal categorization in early oral tongue cancer
- 2021
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Ingår i: Virchows Archiv : an international journal of pathology. - : Springer Science and Business Media LLC. - 1432-2307. ; 478:5, s. 925-932
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Tidskriftsartikel (refereegranskat)abstract
- Stromal categorization has been used to classify many epithelial cancer types. We assessed the desmoplastic reaction and compared its significance with other stromal characteristics in early (cT1-2N0) oral tongue squamous cell carcinoma (OTSCC). In this multi-institutional study, we included 308 cases treated for early OTSCC at five Finnish university hospitals or at the A.C. Camargo Cancer Center in São Paulo, Brazil. The desmoplastic reaction was classified as immature, intermediate, or mature based on the amount of hyalinized keloid-like collagen and myxoid stroma. We compared the prognostic value of the desmoplastic reaction with a stromal grading system based on tumor-stroma ratio and stromal tumor-infiltrating lymphocytes. We found that a high amount of stroma with a weak infiltration of lymphocytes was associated statistically significantly with a worse disease-free survival with a hazard ratio (HR) of 2.68 (95% CI 1.26–5.69), worse overall survival (HR 2.95, 95% CI 1.69–5.15), and poor disease-specific survival (HR 2.66, 95% CI 1.11–6.33). Tumors having a high amount of stroma with a weak infiltration of lymphocytes were also significantly associated with a high rate of local recurrence (HR 4.13, 95% CI 1.67–10.24), but no significant association was found with lymph node metastasis (HR 1.27, 95% CI 0.37–4.35). Categorization of the stroma based on desmoplastic reaction (immature, intermediate, mature) showed a low prognostic value for early OTSCC in all survival analyses (P > 0.05). In conclusion, categorization of the stroma based on the amount of stroma and its infiltrating lymphocytes shows clinical relevance in early OTSCC superior to categorization based on the maturity of stroma.
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| 10. |
- Ammendola, Serena, et al.
(författare)
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The histopathological diagnosis of atypical meningioma: glass slide versus whole slide imaging for grading assessment
- 2021
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Ingår i: Virchows Archiv. - : SPRINGER. - 0945-6317 .- 1432-2307. ; 478, s. 747-756
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Tidskriftsartikel (refereegranskat)abstract
- Limited studies on whole slide imaging (WSI) in surgical neuropathology reported a perceived limitation in the recognition of mitoses. This study analyzed and compared the inter- and intra-observer concordance for atypical meningioma, using glass slides and WSI. Two neuropathologists and two residents assessed the histopathological features of 35 meningiomas-originally diagnosed as atypical-in a representative glass slide and corresponding WSI. For each histological parameter and final diagnosis, we calculated the inter- and intra-observer concordance in the two viewing modes and the predictive accuracy on recurrence. The concordance rates for atypical meningioma on glass slides and on WSI were 54% and 60% among four observers and 63% and 74% between two neuropathologists. The inter-observer agreement was higher using WSI than with glass slides for all parameters, with the exception of high mitotic index. For all histological features, we found median intra-observer concordance of >= 79% and similar predictive accuracy for recurrence between the two viewing modes. The higher concordance for atypical meningioma using WSI than with glass slides and the similar predictive accuracy for recurrence in the two modalities suggest that atypical meningioma may be safely diagnosed using WSI.
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| 11. |
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| 15. |
- Boecker, W., et al.
(författare)
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Multicolor immunofluorescence reveals that p63-and/or K5-positive progenitor cells contribute to normal breast epithelium and usual ductal hyperplasia but not to low-grade intraepithelial neoplasia of the breast
- 2017
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Ingår i: Virchows Archiv. - : Springer Science and Business Media LLC. - 0945-6317 .- 1432-2307. ; 470:5, s. 493-504
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Tidskriftsartikel (refereegranskat)abstract
- We contend that knowledge about the cellular composition of normal breast epithelium is a prerequisite for understanding proliferative breast disease. Against this background, we used multicolor immunofluorescence to study normal breast epithelium and two types of intraepithelial proliferative breast lesion for expression of the p63, basal keratin K5, glandular keratin K8/18, SMA, ER-alpha, and Ki67. We studied eight normal breast epithelium samples, 12 cases of usual ductal hyperplasia, and 33 cases of low-grade intraepithelial neoplasia (9 flat epithelial atypia, 14 low-grade ductal carcinoma in situ and 10 cases of lobular neoplasia). Usual ductal hyperplasia showed striking similarity to normal luminal breast epithelium including p63+ and/or K5+ luminal progenitor cells and the full spectrum of luminal progeny cells. In normal breast epithelium and usual ductal hyperplasia, expression of ER-alpha was associated with lack of expression of the proliferation antigen Ki67. In contrast, we found in both types of low-grade intraepithelial neoplasia robust expression of keratin K8/18 and a positive association between ER-alpha and Ki67 expression. However, these lesions were consistently negative for p63 and/or K5. Our observational study supports the view that usual ductal hyperplasia and low-grade intraepithelial neoplasia are different entities rather than part of a spectrum of the same disease. We propose a new operational model of cell differentiation that may serve to better understand correlations between normal breast epithelium and proliferative breast diseases. From our data we conclude that p63+ and/or K5+ progenitor cells contribute to maintenance of normal epithelium and usual ductal hyperplasia, but not to low-grade intraepithelial neoplasia of the breast.
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| 16. |
- Boecker, W., et al.
(författare)
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Squamous/epidermoid differentiation in normal breast and salivary gland tissues and their corresponding tumors originate from p63/K5/14-positive progenitor cells
- 2015
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Ingår i: Virchows Archiv. - : Springer Science and Business Media LLC. - 0945-6317 .- 1432-2307. ; 466:1, s. 21-36
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Tidskriftsartikel (refereegranskat)abstract
- A small group of tumors of breast and salivary glands contains squamous/epidermoid elements as a constitutive feature (e.g., squamous carcinoma, syringomatous tumors, and mucoepidermoid carcinoma). Other tumors (e.g., pleomorphic adenoma, adenomyoepithelial tumors, and adenoid cystic carcinoma) may show occasionally squamous differentiation. Furthermore, squamous metaplasia may be observed in non-neoplastic breast and salivary tissues. However, the histogenesis of these squamous differentiations is far from being understood. Based on our earlier in situ triple immunofluorescence and quantitative reverse transcription (RT)-PCR experiments for basal keratins K5/14 and p63 as well as for glandular keratins (K7/K8/18), squamous keratins (K10 and K13), and myoepithelial lineage markers (smooth muscle actin, SMA), we here traced the squamous/epidermoid differentiation lineage of 60 tumors of the breast and/or salivary glands, cultured tumor cells of 2 tumors, and of 7 squamous metaplasias of non-neoplastic breast and salivary tissues. Our results indicate that both the neoplastic lesions as well as the non-neoplastic squamous metaplasia contain p63/K5/14+ cells that differentiate toward K10/13+ squamous cells. Thus, cells with squamous/epidermoid differentiation undergo a transition from its original p63/K5/14+ precursor state to K10/13+ squamous lineage state, which can be pictured by triple-immunofluorescence experiments. Given the immunophenotypic similarity of p63/K5/14+ tumor cells to their physiological p63/K5/14+ counterparts in normal breast and salivary duct epithelium, we suggest that these cells provide an important histogenetic key to understanding the pathogenesis of squamous differentiation both in normal breast/salivary gland tissues and their corresponding tumors.
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| 17. |
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| 18. |
- Casar-Borota, Olivera, et al.
(författare)
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KIT protein expression and mutational status of KIT gene in pituitary adenomas
- 2012
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Ingår i: Virchows Archiv. - New York : Springer-Verlag New York. - 0945-6317 .- 1432-2307. ; 460:2, s. 171-181
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Tidskriftsartikel (refereegranskat)abstract
- KIT protein expression and mutational status of KIT gene in different types of tumours have been intensively studied since Imatinib Mesylate, KIT/PDGFRA tyrosine kinase inhibitor became available. However, only one immunohistochemical study on KIT expression in pituitary adenomas has been published. There are currently no reports on mutational status of KIT gene in pituitary adenomas. We have immunohistochemically investigated KIT expression in 252 pituitary adenomas and found cytoplasmic reactivity in 52.4% and membranous reactivity in 8.3% of all adenomas. There was statistically significant difference in KIT expression between clinically non-functioning, growth hormone- and adrenocorticotroph hormone-producing adenomas. The group with membranous expression was dominated by somatotropinomas and clinically non-functioning adenomas. KIT expression in a subset of adenomas was also confirmed by western blot analysis of 48 adenomas. Immunohistochemical KIT expression was correlated with basic clinical data and in a cohort of acromegalic patients with additional data (somatostatin receptor type 2A expression, response to somatostatin analogue treatment and mutational status of gsp oncogene). Exons 9, 11, 13 and 17 of KIT gene were searched for mutations in the tumours with membranous KIT expression and in a minority of tumours with cytoplasmic KIT expression using denaturing high-performance liquid chromatography and in suspected cases sequencing of one or more exons. No mutations in the examined exons were found. Our results may suggest a role of KIT in the pathogenesis of a subset of pituitary adenomas and point out the need for further research to find out if KIT-reactive adenomas could be sensitive to Imatinib Mesylate.
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Cibula, David, et al.
(författare)
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The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology Guidelines for the Management of Patients with Cervical Cancer
- 2018
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Ingår i: Virchows Archiv. - : SPRINGER. - 0945-6317 .- 1432-2307. ; 472:6, s. 919-936
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Tidskriftsartikel (refereegranskat)abstract
- The European Society of Gynecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) jointly develop clinically relevant and evidence-based guidelines in order to improve the quality of care for women with cervical cancer across Europe and worldwide. The ESGO/ESTRO/ESP nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of cervical cancer (23 experts across Europe). To ensure that the guidelines are evidence based, the current literature identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 159 international reviewers, selected through ESGO/ESTRO/ESP and including patient representatives. The guidelines cover comprehensively staging, management, and follow-up for patients with cervical cancer. Management includes fertility sparing treatment; stage T1a, T1b1/T2a1, clinically occult cervical cancer diagnosed after simple hysterectomy; early and locally advanced cervical cancer; primary distant metastatic disease; cervical cancer in pregnancy; and recurrent disease. Principles of radiotherapy and pathological evaluation are defined.
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| 23. |
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| 24. |
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| 25. |
- Cserni, G, et al.
(författare)
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Consistency in recognizing microinvasion in breast carcinomas is improved by immunohistochemistry for myoepithelial markers.
- 2016
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Ingår i: Virchows Archiv: an international journal of pathology. - : Springer Science and Business Media LLC. - 1432-2307. ; 468:4, s. 473-481
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Tidskriftsartikel (refereegranskat)abstract
- Microinvasion is the smallest morphologically identifiable stage of invasion. Its presence and distinction from in situ carcinoma may have therapeutic implications, and clinical staging also requires the recognition of this phenomenon. Microinvasion is established on the basis of several morphological criteria, which may be difficult and not perfectly reproducible among pathologists. The aim of this study was to assess the consistency of diagnosing microinvasion in the breast on traditional haematoxylin and eosin (HE) stained slides and to evaluate whether immunohistochemistry (IHC) for myoepithelial markers could improve this. Digital images were generated from representative areas of 50 cases stained with HE and IHC for myoepithelial markers. Cases were specifically selected from the spectrum of in situ to microinvasive cancers. Twenty-eight dedicated breast pathologists assessed these cases at different magnifications through a web-based platform in two rounds: first HE only and after a washout period by both HE and IHC. Consistency in the recognition of microinvasion significantly improved with the use of IHC. Concordance rates increased from 0.85 to 0.96, kappa from 0.5 to 0.85, the number of cases with 100 % agreement rose from 9/50 to 25/50 with IHC and the certainty of diagnosis also increased. The use of IHC markedly improves the consistency of identifying microinvasion. This corroborates previous recommendations to use IHC for myoepithelial markers to clarify cases where uncertainty exists about the presence of microinvasion. Microinvasive carcinoma is a rare entity, and seeking a second opinion may avoid overdiagnosis.
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| 26. |
- Dorofte, Luiza, 1982-, et al.
(författare)
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Low level of interobserver concordance in assessing histological subtype and tumor grade in patients with penile cancer may impair patient care
- 2022
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Ingår i: Virchows Archiv. - : Springer. - 0945-6317 .- 1432-2307. ; 480:4, s. 879-886
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Tidskriftsartikel (refereegranskat)abstract
- Differentiation between penile squamous cell carcinoma patients who can benefit from limited organ-sparing surgery and those at significant risk of lymph node metastasis is based on histopathological prognostic factors including histological grade and tumor histological subtype. We examined levels of interobserver and intraobserver agreement in assessment of histological subtype and grade in 207 patients with penile squamous cell carcinoma. The cases were assessed by seven pathologists from three hospitals located in Sweden and Italy. There was poor to moderate concordance in assessing both histological subtype and grade, with Fleiss kappas of 0.25 (range: 0.02-0.48) and 0.23 (range: 0.07-0.55), respectively. When choosing HPV-associated and non-HPV-associated subtypes, interobserver concordance ranged from poor to good, with a Fleiss kappa value of 0.36 (range: 0.02-0.79). A re-review of the slides by two of the pathologists showed very good intraobserver concordance in assessing histological grade and subtype, with Cohen's kappa values of 0.94 and 0.91 for grade and 0.95 and 0.84 for subtype. Low interobserver concordance could lead to undertreatment and overtreatment of many patients with penile cancer, and brings into question the utility of tumor histological subtype and tumor grade in determining patient treatment in pT1 tumors.
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| 27. |
- Dorofte, L, 1982-, et al.
(författare)
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Reliability of histological subtyping of penile squamous cell carcinoma in assessing HPV tumour status
- 2022
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Ingår i: Virchows Archiv. - : Springer. - 0945-6317 .- 1432-2307. ; 481:Suppl. 1, s. S168-S168
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background & objectives: HPV-positive penile tumours have been associated with higher survival rates. However, HPV analysis is unavailable in many low-income countries. We investigated if histological assessment of penile squamous cell carcinoma subtypes can replace HPV testing in determining HPV-related/non-HPV-related tumour status.Methods: We reviewed paraffin-embedded tumour tissue from 345 penile cancer patients, surgically treated between 2009 and 2018 at Örebro University Hospital, Sweden. The histological subtype of squamous cell carcinoma was assessed according to the WHO criteria and ISUP recommendations. HPV-DNA genotyping was performed using the PCR method Anyplex II HPV28. Concordance was assessed by calculating Cohen’s kappa (κ).Results: A good concordance was found between histological subtype of squamous cell carcinoma and HPV tumour-status with a Cohen’s kappa (κ) of 0,72 corresponding to 86,6% agreement. Of the 46 discordant cases, five had HPV-related histology (mixed subtypes) but were HPV-negative. The remaining 41 cases had non-HPV- related histology (85% usual subtype, 15% mixed subtypes) but were HPV-positive. Noteworthy is that in 21 of the cases with non-HPV-related histology, foci of undifferentiated PeIN was found. In addition, four cases with both undifferentiated PeIN and lichen sclerosus et atrophicus in the tumour margin, 14 cases with both differentiated PeIN and lichen sclerosus et atrophicus and two cases without preneoplastic lesion were identified.Conclusion: Good concordance between histological subtype of penile squamous cell carcinoma and HPV genotyping shows that when necessary, histological assessment is a good alternative, at least in less resourceful settings, to PCR-based HPV analysis in determining if penile tumours are HPV or non-HPV-related. Discordant cases most likely depend on subjectivity in histological assessment but can also suggest a HPV infection in a non-HPV-related tumour.
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| 28. |
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| 29. |
- D'Souza, MA, et al.
(författare)
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Redefining resection margins and dissection planes in perihilar cholangiocarcinoma-radical resection is a rare event
- 2022
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Ingår i: Virchows Archiv : an international journal of pathology. - : Springer Science and Business Media LLC. - 1432-2307. ; 480:3, s. 557-564
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Tidskriftsartikel (refereegranskat)abstract
- Radical tumor resection (pR0) is prognostic for disease-free and overall survival after resection of perihilar cholangiocarcinoma (pCCA). However, no universal agreement exists on the definition of radical resection and histopathological reporting. The aim of this study was to provide a standardized protocol for histopathological assessment and reporting of the surgical specimen obtained after resection for pCCA. All consecutive patients operated for pCCA with curative intent at the Karolinska University Hospital, Stockholm, Sweden between 2012 and 2021 were included. A standardized protocol for histopathological assessment and reporting of the surgical specimen after liver resection for pCCA is presented. A detailed mapping of the transection margins and dissection planes was performed. The results of applying different existing pR0 definitions were compared. Sixty-eight patients with pCCA were included. Five transection margins and two dissection planes were defined. By defining pR0 as cancer-free margins and planes tolerating distances <1mm, the pR0 rate was 66%. However, when pR0 was set as >1mm from invasive cancer to all resection margins and dissection planes, the pR0 rate fell to 16%. This study supports the use of thorough and standardized pathological handling, assessment and reporting of resection margins and dissection planes of surgical specimens of pCCA.
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| 30. |
- Egevad, L, et al.
(författare)
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Identification of areas of grading difficulties in prostate cancer and comparison with artificial intelligence assisted grading
- 2020
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Ingår i: Virchows Archiv : an international journal of pathology. - : Springer Science and Business Media LLC. - 1432-2307. ; 477:6, s. 777-786
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Tidskriftsartikel (refereegranskat)abstract
- The International Society of Urological Pathology (ISUP) hosts a reference image database supervised by experts with the purpose of establishing an international standard in prostate cancer grading. Here, we aimed to identify areas of grading difficulties and compare the results with those obtained from an artificial intelligence system trained in grading. In a series of 87 needle biopsies of cancers selected to include problematic cases, experts failed to reach a 2/3 consensus in 41.4% (36/87). Among consensus and non-consensus cases, the weighted kappa was 0.77 (range 0.68–0.84) and 0.50 (range 0.40–0.57), respectively. Among the non-consensus cases, four main causes of disagreement were identified: the distinction between Gleason score 3 + 3 with tangential cutting artifacts vs. Gleason score 3 + 4 with poorly formed or fused glands (13 cases), Gleason score 3 + 4 vs. 4 + 3 (7 cases), Gleason score 4 + 3 vs. 4 + 4 (8 cases) and the identification of a small component of Gleason pattern 5 (6 cases). The AI system obtained a weighted kappa value of 0.53 among the non-consensus cases, placing it as the observer with the sixth best reproducibility out of a total of 24. AI may serve as a decision support and decrease inter-observer variability by its ability to make consistent decisions. The grading of these cancer patterns that best predicts outcome and guides treatment warrants further clinical and genetic studies. Results of such investigations should be used to improve calibration of AI systems.
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| 31. |
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| 32. |
- Egevad, Lars, et al.
(författare)
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Interobserver reproducibility of perineural invasion of prostatic adenocarcinoma in needle biopsies
- 2021
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Ingår i: Virchows Archiv. - : Springer Nature. - 0945-6317 .- 1432-2307. ; 478:6, s. 1109-1116
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Tidskriftsartikel (refereegranskat)abstract
- Numerous studies have shown a correlation between perineural invasion (PNI) in prostate biopsies and outcome. The reporting of PNI varies widely in the literature. While the interobserver variability of prostate cancer grading has been studied extensively, less is known regarding the reproducibility of PNI. A total of 212 biopsy cores from a population-based screening trial were included in this study (106 with and 106 without PNI according to the original pathology reports). The glass slides were scanned and circulated among four pathologists with a special interest in urological pathology for assessment of PNI. Discordant cases were stained by immunohistochemistry for S-100 protein. PNI was diagnosed by all four observers in 34.0% of cases, while 41.5% were considered to be negative for PNI. In 24.5% of cases, there was a disagreement between the observers. The kappa for interobserver variability was 0.67-0.75 (mean 0.73). The observations from one participant were compared with data from the original reports, and a kappa for intraobserver variability of 0.87 was achieved. Based on immunohistochemical findings among discordant cases, 88.6% had PNI while 11.4% did not. The most common diagnostic pitfall was the presence of bundles of stroma or smooth muscle. It was noted in a few cases that collagenous micronodules could be mistaken for a nerve. The distance between cancer and nerve was another cause of disagreement. Although the results suggest that the reproducibility of PNI may be greater than that of prostate cancer grading, there is still a need for improvement and standardization.
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| 33. |
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| 34. |
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| 35. |
- Ehinger, Anna, et al.
(författare)
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Myoepithelium assessment with p63 immunostaining in formalinfixed paraffin-embedded breast cancer tissue pre-treated with RNA-later
- 2017
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Ingår i: Virchows Archiv. - : Springer Science and Business Media LLC. - 1432-2307 .- 0945-6317. ; 471:Supplement 1, s. 299-299
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Konferensbidrag (refereegranskat)abstract
- Objective: To assessmyoepithelium with p63 in fresh breast cancer (BC)tissue samples collected in RNA later for further analysis with NextGeneration Sequencing (NGS) technique. For a better understanding ofthe NGS bulk-analysis, a central part of the sample in RNA-later isformalin-fixed paraffin-embedded to score relative cellularity in % onhematoxylin-eosin (HE) staining (% of invasive cancer, cancer in situ,benign epithelium, lymphocytes and fat). Our aim is hence to test p63immunohistochemistry (IHC) to highlight myoepithelium and to facilitatethe evaluation of the relative cellularity on BC-tissue pre-treated withRNA-later.Method: Two-hundred and twenty-four selected samples of fresh BCtissue collected in RNA-later. A 10 mg central piece from each samplewas FFPE and assembled in a tissue-microarray (TMA) and sectioned toHE and p63 IHC.Results: All samples (n = 224) had internal control for myoepitheliumsurrounding in situ cancer or benign epithelium. p63 showed positivenuclear staining in myoepithelial cells in 92 % (206/224) of samplesand false negative p63 staining in 8 % (18/224).Conclusion: p63 IHC is assessable in samples of FFPE BC-tissue pretreatedwith RNA-later.
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| 36. |
- Ehinger, Anna, et al.
(författare)
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Quality of up to 35 years old archival breast cancer tissue in paraffinblocks for estrogen receptor evaluation
- 2017
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Ingår i: Virchows Archiv. - : Springer Science and Business Media LLC. - 1432-2307 .- 0945-6317. ; 471:Suppl. 1, s. 54-54
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Konferensbidrag (refereegranskat)abstract
- Objective: Estrogen receptor (ER) positive breast cancer (BC) can havean insidious course with disease-relapse decades after primary surgery.New analysis performed on archived formalin-fixed paraffin-embedded(FFPE) tissue are important for disease-management in late BC-relapseand an important tool in BC-research. However, although loss of immunoreactivityin tissue slides after sectioning has been shown, little isknown of the preservation of biomarker-expression in FFPE tumourblocks.We aim to investigate the quality of immunohistochemical(IHC) ER-evaluation in FFPE-tissue over time (1978–2000).Method: Tissue-microarrays from a Swedish multicenter cohort of 728patients with contralateral BC was used for ER IHC-evaluation. BC wasstudied in three periods (1958–1985, 1986–1993, 1994–2000), and retrospectiveER IHC-data was correlated to corresponding prospective ERcytosol-analysis performed on fresh BC-tissue.Results: The concordance between the original ER cytosol-analysis andthe new IHC was substantial (1978–1985: 82 %, (117/142), Kappa 0.52.1986–1993: 91 %, (194/213), Kappa 0.72. 1994–2000: 86 %, (187/218),Kappa 0.61). Discrepancies were mostly found for tumours with ERvaluesclose to cutoff for one or both of the methods.Conclusion: FFPE BC-tissue from the late 70s to millennium showspreserved ER-antigenicity up to 35 years later.
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| 37. |
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| 38. |
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| 39. |
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| 40. |
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| 41. |
- Fehr, Andre, et al.
(författare)
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Mucoepidermoid carcinoma of the salivary glands revisited with special reference to histologic grading and CRTC1/3-MAML2 genotyping.
- 2021
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Ingår i: Virchows Archiv : an international journal of pathology. - : Springer Science and Business Media LLC. - 1432-2307. ; 479, s. 975-985
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Tidskriftsartikel (refereegranskat)abstract
- Mucoepidermoid carcinoma (MEC) is the most common carcinoma of the salivary glands. Here, we have used two large patient cohorts with MECs comprising 551 tumors to study clinical, histological, and molecular predictors of survival. One cohort (n=167), with known CRCT1/3-MAML2 fusion status, was derived from the Hamburg Reference Centre (HRC; graded with the AFIP and Brandwein systems) and the other (n=384) was derived from the population-based Cancer Registry of North Rhine-Westphalia (LKR-NRW; graded with the AFIP system). The reliability of both the AFIP and Brandwein grading systems was excellent (n=155). The weighted kappa for inter-rater agreement was 0.81 (95% CI 0.65-0.97) and 0.83 (95% CI 0.71-0.96) for the AFIP and Brandwein systems, respectively. The 5-year relative survival was 79.7% (95% CI 73.2-86.2%). Although the Brandwein system resulted in a higher rate of G3-MECs, survival in G3-tumors (AFIP or Brandwein grading) was markedly worse than in G1/G2-tumors. Survival in>T2 tumors was markedly worse than in those with lower T-stage. Also, fusion-negative MECs had a worse 5-year progression-free survival. The frequency of fusion-positive MECs in the HRC cohort was 78.4%, of which the majority (86.7%) was G1/G2-tumors. In conclusion, the AFIP and Brandwein systems are useful in estimating prognosis and to guide therapy for G3-MECs. However, their significance regarding young age (≤30years) and location-dependent heterogeneity of in particular G2-tumors is more questionable. We conclude that CRTC1/3-MAML2 testing is a useful adjunct to histologic scoring of MECs and for pinpointing tumors with poor prognosis with higher precision, thus avoiding overtreatment.
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| 42. |
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| 43. |
- Friberg, Niklas, et al.
(författare)
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Cause of death and significant disease found at autopsy
- 2019
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Ingår i: Virchows Archiv. - : SPRINGER. - 0945-6317 .- 1432-2307. ; 475:6, s. 781-788
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Tidskriftsartikel (refereegranskat)abstract
- The use of clinical autopsy has been in decline for many years throughout healthcare systems of developed countries despite studies showing substantial discrepancies between autopsy results and pre-mortal clinical diagnoses. We conducted a study to evaluate over time the use and results of clinical autopsies in Sweden. We reviewed the autopsy reports and autopsy referrals of 2410 adult (age > 17) deceased patients referred to two University hospitals in Sweden during two plus two years, a decade apart. There was a decline in the number of autopsies performed over time, however, mainly in one of the two hospitals. The proportion of autopsy referrals from the emergency department increased from 9 to 16%, while the proportion of referrals from regular hospital wards was almost halved. The autopsies revealed a high prevalence of cardiovascular disease, with myocardial infarction and cerebrovascular lesion found in 40% and 19% of all cases, respectively. In a large proportion of cases (> 30%), significant findings of disease were not anticipated before autopsy, as judged from the referral document and additional data obtained in some but not all cases. In accordance with previous research, our study confirms a declining rate of autopsy even at tertiary, academic hospitals and points out factors possibly involved in the decline.
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- Garvin, Stina, et al.
(författare)
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Differences in intra-tumoral macrophage infiltration and radiotherapy response among intrinsic subtypes in pT1-T2 breast cancers treated with breast-conserving surgery
- 2019
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Ingår i: Virchows Archiv. - : SPRINGER. - 0945-6317 .- 1432-2307. ; 475:2, s. 151-162
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer (BC) intrinsic subtype classification is based on the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and proliferation marker Ki-67. The expression of these markers depends on both the genetic background of the cancer cells and the surrounding tumor microenvironment. In this study, we explore macrophage traits in cancer cells and intra-tumoral M2-macrophage infiltration (MI) in relation to intrinsic subtypes in non-metastatic invasive BC treated with breast conserving surgery, with and without postoperative radiotherapy (RT). Immunostaining of M2-macrophage-specific antigen CD163 in cancer cells and MI were evaluated, together with ER, PR, HER2, and Ki-67-expression in cancer cells. The tumors were classified into intrinsic subtypes according to the ESMO guidelines. The immunostaining of these markers, MI, and clinical data were analyzed in relation to ipsilateral local recurrence (ILR) as well as recurrence-free (RFS) and disease-free specific (DFS) survival. BC intrinsic subtypes are associated with T-stage, Nottingham Histologic Grade (NHG), and MI. Macrophage phenotype in cancer cells is significantly associated with NHG3-tumors. Significant differences in macrophage infiltration were observed among the intrinsic subtypes of pT1-T2 stage BC. Shorter RFS was observed in luminal B HER2neg tumors after RT, suggesting that this phenotype may be more resistant to irradiation. Ki-67-expression was significantly higher in NHG3 and CD163-positive tumors, as well as those with moderate and high MI. Cancer cell ER expression is inversely related to MI and thus might affect the clinical staging and assessment of BC.
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