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| 2. |
- Gudjonsson, Sigurdur, et al.
(författare)
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The Value of the UroVysion((R)) Assay for Surveillance of Non-Muscle-Invasive Bladder Cancer.
- 2008
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 54:2, s. 402-408
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Patients with non-muscle-invasive bladder cancer are traditionally followed by repeat cystoscopy and urine cytology. A fluorescence in situ hybridisation technique called UroVysion((R)) (UV) is now available for clinical diagnosis of urothelial cancer cells. The aim of the present study was to compare UV analysis with routine follow-up methods. METHODS: We studied an unselected cohort of patients undergoing cystoscopy follow-ups at two Swedish centres in 2004-2005. All patients were investigated by cystoscopy, cytology, and UV assay. The UV assay was evaluated with regards to sensitivity, specificity, and positive predictive value for tumour recurrence. RESULTS: In all, 159 cases were analysed. UV had a 30% overall sensitivity for the 27 biopsy-proven recurrences and 70% sensitivity for high-risk tumours (pT1 and carcinoma in situ [CIS]). The specificity of UV was 95%. UV detected all six CIS cases in the study and was predictive in two additional patients who developed CIS within 1 yr of inclusion. Cytology was positive in four of those eight CIS cases and atypical in the other four. CONCLUSIONS: The UV assay cannot replace cystoscopy for surveillance of patients with non-muscle-invasive bladder cancer, but it may be valuable as a supplement to traditional measures for detecting CIS. Before any conclusions can be drawn regarding the efficacy of novel markers of bladder cancer, they must be studied in bladder cancer patients undergoing endoscopic surveillance.
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| 3. |
- Isfoss, Björn, et al.
(författare)
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Distribution of aldehyde dehydrogenase 1-positive stem cells in benign mammary tissue from women with and without breast cancer.
- 2012
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Ingår i: Histopathology. - : Wiley. - 0309-0167. ; 60:4, s. 617-633
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Tidskriftsartikel (refereegranskat)abstract
- Isfoss B L, Holmqvist B, Alm P & Olsson H (2012) Histopathology Distribution of aldehyde dehydrogenase 1-positive stem cells in benign mammary tissue from women with and without breast cancer Aims: Aldehyde dehydrogenase 1 (ALDH1) in female breast tissue has been linked to stem cells, but little is known about the benign cellular organization in situ. We investigated the distribution of ALDH1-immunoreactive (ALDH1+) cells in histomorphologically benign breast tissue from 28 women with or without breast cancer. Methods and results: ALDH1+ cells were detected in benign tissue of women aged 20-72 years, located most commonly at the luminal and intermediate ductular levels and in the stroma. ALDH1+ cell populations and Ki67+ cell populations were present in separate ductules, both cell types rarely showing epithelial differentiation. ALDH1+ cells were non-reactive to Ki67 and oestrogen receptor. Stromal round/oval ALDH1+ non-leukocyte cells in both age groups expressed contractile protein. There was a lower concentration of luminal and intermediate ductular ALDH1+ cells in postmenopausal women than in premenopausal women, and in cancer patients than in non-cancer patients, and a higher concentration in women receiving exogenous hormones. Conclusions: This study provides further evidence for the stem cell character of ALDH1+ cells, here in benign breast tissue of cancer and non-cancer patients throughout non-lactating adult life, and contributes evidence of benign stromal ALDH1+ cells. The distribution of ductular ALDH1+ stem cells appears to be influenced by hormonal status.
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| 4. |
- Isfoss, Björn
(författare)
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Histologic characterization of stem cells in mammary epithelium and stroma
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- It is unknown whether native cells in benign breast tissue mediate risk of cancer.We therefore aimed to identify cell types in benign human mammary tissueimmunohistologically using markers of stemness and differentiation, and toinvestigate their possible associations with clinical risk factors for breast cancer.We found that cells that are integrated in benign epithelium and areimmunoreactive for the stem cell marker ALDH1 are negative for markers ofglandular differentiation, proliferation, and estrogen receptor. High numbers ofthese cells were associated with the risk factors family history of breast cancer,BRCA1/2 carrier status, low parity, and hormone use.Stromal ALDH1+ cells are either spindle-shaped/polygonal (s/p) or round/oval(r/o), and the latter are positive for the contractile protein marker SMMHC.ALDH1+ s/p cells are positive for the stellate cell marker vinculin. Low numbersof these cells were associated with family history, and when negative for the stemcell marker CD44 they were associated with nulliparity. Low numbers ofALDH1+ CD44+ CD24– r/o cells were associated with family history. ALDH1+r/o cells were positively or negatively associated with low parity depending on thepatients' BRCA1/2 status.High numbers of r/o cells that are positive for the mesenchymal stem cellmarker SSEA3 were associated with low parity, family history, and hormone useafter menopause.This study describes novel stromal cells in breast that were associated with riskfactors for breast cancer. If confirmed in independent cohorts, they may be usedfor stratification of women with regard to risk of breast cancer.
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| 5. |
- Isfoss, Björn L, et al.
(författare)
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Diagnosis of intraurothelial neoplasia : Interobserver variation and the value of individual histopathologic attributes
- 2011
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Ingår i: Analytical and Quantitative Cytology and Histology. - 0884-6812. ; 33:2, s. 75-81
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine interobserver variation in histopathologic diagnosis of carcinoma in situ (CIS) and dysplasia (collectively intraurothelial neoplasia [IUN]) of the bladder and identify histomorphologic features important for diagnosis. STUDY DESIGN: A total of 272 consecutive bladder tissue samples were re-evaluated blindly by two general pathologists and one uropathologist for IUN. Discrepancies were resolved jointly. Fifteen histopathologic attributes were evaluated for prediction of diagnosis. Followup revealed recurrence and progression rates for each diagnostic category. RESULTS: Thirty-six percent of specimens contained no evaluable flat mucosa; 51% percent of specimens from papillary urothelial neoplasia (PUN) cases showed CIS. General pathologists detected 56-69% of CIS and 8-42% of dysplasia. Histopathologic features most predictive for CIS were nuclear size, variation in nuclear shape, loss of maturation, loss of polarity, and architectural disorder. None of these individually or in combination exceeded general pathologists' diagnostic accuracy. IUN was not predictive of recurrence or progress. CONCLUSION: Using material mostly consisting of flat mucosa gratuitously provided in PUN resection specimens, IUN carries no prognostic value. General histopathologists detect IUN poorly to moderately, and the five most discriminatory histomorphologic features are insufficient for diagnosis. Interobserver agreement for dysplasia is dismal. Absent flat mucosa in PUN resections predicts recurrence.
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| 6. |
- Isfoss, Björn L, et al.
(författare)
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Simplification of grading papillary urothelial neoplasia using a reduced set of diagnostic features
- 2011
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Ingår i: Analytical and Quantitative Cytology and Histology. - 0884-6812. ; 33:2, s. 68-74
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine whether a reduced set of the histopathologic features used in internationally accepted classifications is capable of accurately grading papillary urothelial neoplasms (PUN). STUDY DESIGN: All surgical specimens from urinary bladders received during a 2-year period were reexamined by an expert uropathologist for assessing the accuracy of original nonexpert PUN grading and staging. Thirteen histopathologic features entailing 32 attributes were evaluated with regard to prediction of expert grade. Patients were followed for 35-59 months (mean, 47). RESULTS: A total of 88 PUN specimens could be analyzed completely including follow-up specimens. Agreement between original and expert grade was 71% for low-grade and 87% for high-grade PUN, with overall kappa = 0.53. The histomorphologic features most predictive of expert grade were architectural disorder, variability of nuclear enlargement, and absence of umbrella cells. Neither individual histomorphologic attributes nor their combinations were as predictive of expert pathologist grade as original diagnoses. CONCLUSION: Improvements in PUN grading and prognostication are not likely to be accomplished by only reducing the number of histomorphologic features currently recommended by the World Health Organization and International Society of Urological Pathology.
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| 7. |
- Isfoss, Björn Logi, et al.
(författare)
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Stellate cells and mesenchymal stem cells in benign mammary stroma are associated with risk factors for breast cancer - an observational study
- 2018
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is not known whether stromal cells in benign breast tissue can mediate risk of breast cancer. We recently described aldehyde dehydrogenase 1 A1 (ALDH1) positive (+) cells in morphologically normal breast stroma of premenopausal women, and the data indicated that their distribution is associated with clinical risk factors for breast cancer. The aim of the present study was to define the identities of these cells using histologic and immunohistologic methods, and to investigate associations between those cells and hormonal and genetic risk factors in pre- and postmenopausal women. Methods: Stroma of morphologically normal tissue was analyzed in samples from 101 well-characterized women whose breasts had been operated. Morphology and immunolabeling were applied to determine cell identities based on the putative stem cell markers ALDH1 and stage-specific embryonic antigen-3 (SSEA3), and immunophenotypes indicating mast cells or stellate cells. The results were compared with the patients' risk factors using regression analysis (two-tailed). Results: ALDH1+ round/oval cells were associated with low parity in BRCA1/2 carriers (p=0.022), while in non-BRCA1/2-carriers they were negatively associated with nulliparity (p=0.057). In premenopausal women ALDH1+ round/oval cells were associated with family history (p=0.058). SSEA3+ round/oval cells were morphologically and immunohistologically consistent with multilineage stress-enduring (Muse) cells, and these cells were independently associated with the breast cancer risk factors low parity (p=0.015), family history (p=0.021), and hormone use after menopause (p=0.032). ALDH1+ spindle-shaped/polygonal cells were immunohistologically consistent with stellate cells, and were negatively associated with family history of breast cancer (p=0.001). Conclusion: This study identified novel stromal cell types in benign breast tissue that have a potential for stratifying women for breast cancer risk.
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| 8. |
- Isfoss, Björn Logi, et al.
(författare)
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The absence of aldehyde dehydrogenase 1 A1-positive cells in benign mammary stroma is associated with risk factors for breast cancer
- 2016
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Ingår i: Breast Cancer: Targets and Therapy. - 1179-1314. ; 8, s. 117-124
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Tidskriftsartikel (refereegranskat)abstract
- In this study, aldehyde dehydrogenase 1 (ALDH1)-expressing cells in stroma of histologically normal breast tissue from premenopausal women were investigated in situ regarding cellular morphology, cell distribution, and relation to the additional stem cell markers, CD44 (+) and CD24 (-). These results were correlated with hormonal and genetic risk factors for breast cancer. Triple immunofluorescence labeling was performed on tissues from premenopausal women with a family history of breast cancer, and breast reduction specimens from premenopausal women with no family history of breast cancer were used as a control group. The majority of ALDH1-immunoreactive cells in stroma were spindle-shaped or polygonal, and such cells that were CD44- and CD24- were absent in the breast stroma of a significantly larger number of nulliparous than parous women. A less common morphological type of ALDH1-positive cells in stroma was round or oval in shape, and such cells that were CD44+ and CD24- were absent in a significant number of women with a family history of breast cancer. The CD44+/CD24- immunophenotype is consistent with stem cells, and the round/oval morphology suggests mesenchymal cells. This study demonstrates that there are two morphologically distinct types of ALDH1-positive cells in histologically benign mammary stroma, and the absence of these cells is correlated with clinical risk factors for breast cancer in premenopausal women.
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| 9. |
- Isfoss, Björn L, et al.
(författare)
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Women with familial risk for breast cancer have an increased frequency of aldehyde dehydrogenase expressing cells in breast ductules
- 2013
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Ingår i: BMC Clinical Pathology. - : Springer Science and Business Media LLC. - 1472-6890. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Knowledge is limited regarding the association between stem cells in histologically benign breast tissue and risk factors for breast cancer, and hence we addressed this issue in the present study. Recently, we assessed the histology of benign breast tissue from cancer and non-cancer patients for cells positive for the putative stem cell marker aldehyde dehydrogenase 1 A1 (ALDH), and the findings indicated an association between expression of ALDH and the hormonal factors menopause and hormone therapy. The current investigation examined possible associations between various known clinical and genetic risk factors for breast cancer and cellular expression of ALDH in ductules in benign human breast tissue.METHODS: The study included breast surgery patients that were BRCA1/2 mutation carriers without breast cancer (n = 23), had BRCA1/2 (n = 28) or sporadic (n = 21) breast cancer, or required non-cancer-related mammoplasty (n = 34). The distribution and frequency of ALDH-immunolabelled cells were correlated to patient subgroups with different risk factors, using mammoplasty patients as a control group. Statistical analyses comprised linear and logistic regression, Spearman's rank test, Pearson's test, and Fisher's exact test. In two-tailed tests, p < 0.05 was considered significant.RESULTS: A strong association was found between family history of breast cancer and a high frequency of ALDH+ cells (p = 0.001) at all ductular levels in all groups, regardless of BRCA status, age, parity, or occurrence of cancer. In pre-menopausal non-BRCA cancer patients, the frequency of ALDH+ cells increased with age (p < 0.01) but decreased with increasing parity (p < 0.03). High frequencies of ALDH+ cells were found in the non-basal ductular levels in BRCA1 mutation carriers (p = 0.03), but in the basal ductular level in BRCA2 cancer patients (p = 0.02). Among post-menopausal patients, only on-going hormone replacement therapy was correlated with a high number of ALDH+ cells (p < 0.03).CONCLUSION: In histologically normal breast tissue, we found a positive association between the frequency of ductular ALDH+ cells and several breast cancer risk factors, particularly family history of this disease, which supports previous evidence that ALDH plays a role in breast cancer.
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