| 1. |
- Oda, Husam, 1975-
(författare)
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Leucine-rich repeats and immunoglobulin-like domain (LRIG) proteins : possible prognostic markers in vulvar squamous cell carcinoma, endometrial carcinoma, and oropharymgeal squamous cell carcinoma
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The human leucine-rich repeats and immunoglobulin-like domain (LRIG) gene family comprises three genes, LRIG1, LRIG2 and LRIG3, which encode the LRIG1, LRIG2 and LRIG3 proteins, respectively. Previous stidies have revealed the different prognostic roles of these proteins in different cancers, and it has been shown that LRIG1 functions as a tumour suppressor in certain cancers via its negative regulation of several receptor tyrosine kinases. Much less is known about the functionof LRIG2 and LRIG3. The expression of all three LRIG genes has been studied with human papillomavirus (HPV). In particular, expression of LRIG1 has been associated with improved survival in cervical, vaginal, and oropharyngeal cancers. Since LRIG1 has been shown to predict sensitivity to paltinum-based chemotherapy when studied in different cell lines, the possible role of LRIG protein expression in HPV-associated and other cancers may be interesting to investigate furthur.The overall aim of this thesis was to evaluate the immunoreactivity of LRIGs in vulvar squamous cell carcinoma (VSCC), endometrial carcinoma (EC) and oropharyngeal squamous cell carcinoma (OPSCC) and to investigate the potential prognostic value of LRIG proteins in association with HPV and p16 status in VSCC and OPSCC and to investigate the possible prognostic value of LMO7 and other prognostic markers of interest. Expression of the LRIG proteins and other markers was evaluated with immunohistochemistry, and HPV status was determined by PCR.In VSCC, high immunoreactivity of LRIG2 and LMO7 was associated with good survival. LRIG1 was not a significant prognostic factor in VSCC. We also conducted a pilot study to evaluate the immunoreactivity of LRIG proteins in 75 women with EC. Most of the patients in this cohort had very high positivity for LRIG proteins. High expression of LRIG3 was associated with better survival. LRIG1 and LRIG2 expression in tumours had no impact on prognosis in this study, but this should be interpreted with great caution due to the limited size of the cohort. Finally, high expression of LMO7 was associated with improved survival in OPSCC. In this cohort of 143 patients, LRIG1 expression was associated with worse survival in HPV-driven tumours. This is in contrast to previous published work where high LRIG1 expression has been associated with good survival. Notably, in both the VSCC and OPSCC cohort, a new polyclonal LRIG1 antibody was used in contrast to that in a previous study of OPSCC.In conclusion, we report additional data on the prognosticvalue of LRIG proteins in smaller cohort of VSCC, EC and OPSCC and suggest that these molecular markers need to be investigated furthur to elucidate possible clinical implications. In addition, a new monoclonal antibody against LRIG1 needs to be developed to ensure the reproducibility of the data.
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| 2. |
- Danielsson, Johanna, et al.
(författare)
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Medical students’ experiences in learning to perform pelvic examinations : a mixed-methods study
- 2021
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Ingår i: International Journal of Medical Education. - Nottingham : Medical Education Unit University of Nottingham. - 2042-6372. ; 12, s. 233-242
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: We aimed to explore learning experiences among medical students learning to perform pelvic examinations and to identify factors that facilitate their training.Methods: A mixed-methods study including a web-based survey and focus group discussions (FGDs) was conducted among medical students who had completed their obstetrics and gynaecology (ObGyn) clerkship. The FGDs were recorded, transcribed and analysed using qualitative content analysis with systematic text condensation. Survey factors were compared using the χ2 test or Fisher's exact test.Results: 160 students (97 female, 61 male, two other) at six universities in Sweden responded to the survey. Two mixed FGDs were conducted. The majority (87%) of the students experienced confidence in performing pelvic examinations, stating that sufficient, repeated training opportunities and support from a clinical tutor were crucial components of the learning experience. Prior to the ObGyn clerkship, negative expectations were more common among male students. The male participants experienced having a disadvantage because of their gender, while female students considered their gender an advantage (p<0.001, N=121, Fisher's Exact Test). The clinical tutor and the use of professional patients (PPs) had a fundamental role in providing learning opportunities by including the student in patient care activities.Conclusions: The importance of the clinical tutor, as well as the use of PPs, are important factors when planning education in pelvic examinations, and this knowledge could be used when educating other intimate examinations during medical school. In addition, similar investigations on students' experience in training other intimate examinations could be considered.
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| 3. |
- Green, Caroline, et al.
(författare)
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Combined treatment with radiotherapy, chemotherapy and avelumab results in regression of metastatic Merkel cell carcinoma and improvement of associated Lambert‑Eaton myasthenic syndrome : a case report
- 2022
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 24:5
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Tidskriftsartikel (refereegranskat)abstract
- Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine malignancy arising from mecha‑ noreceptors in the basal epidermis. Due to a pronounced risk of spread and a high propensity for recurrence after treatment, immediate treatment is of utmost importance. Lambert‑Eaton myasthenic syndrome (LEMS) is a paraneoplastic phenom‑ enon affecting the muscles with autoimmune pathophysiology, and >50% of known cases are associated with an underlying malignancy. In the present report, the case of a 67‑year‑old man presenting with progressive proximal muscle weakness, auto‑ nomic dysfunction and involuntary weight loss is described. Symptoms and detection of voltage‑gated calcium channel antibodies were consistent with LEMS. Distant metastases were found in the inguinal and iliac lymph nodes, and these were immunohistochemically confirmed to be of epithelial and neuroendocrine origin, consistent with MCC. Local radio‑ therapy and chemotherapy improved the symptoms; however, a change of treatment was required due to the side effects of the chemotherapy. Avelumab, an immune checkpoint inhibitor, was therefore introduced, and within a year the patient did not only experience tumor remission but also exhibited marked improvements in muscle strength and mobility. At present, 2 years later, the MCC is still in remission. To the best of our knowledge, the present report is the first to describe MCC with associated LEMS, which was successfully treated with avelumab after previous radiotherapy and chemotherapy, with both improved functional motor recovery and tumor reduc‑ tion. In conclusion, the present case report demonstrated that the present treatment strategy is a potential treatment option and could thus be considered in similar cases.
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| 4. |
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| 5. |
- Israelsson, Pernilla, et al.
(författare)
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Immunoreactivity of LMO7 and other molecular markers as potential prognostic factors in oropharyngeal squamous cell carcinoma
- 2024
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Ingår i: BMC Oral Health. - : BioMed Central (BMC). - 1472-6831. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite the better prognosis associated with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), some patients experience relapse and succumb to the disease; thus, there is a need for biomarkers identifying these patients for intensified treatment. Leucine-rich repeats and immunoglobulin-like domain (LRIG) protein 1 is a negative regulator of receptor tyrosine kinase signaling and a positive prognostic factor in OPSCC. Studies indicate that LRIG1 interacts with the LIM domain 7 protein (LMO7), a stabilizer of adherence junctions. Its role in OPSCC has not been studied before.Methods: A total of 145 patients diagnosed with OPSCC were enrolled. Immunohistochemical LMO7 expression and staining intensity were evaluated in the tumors and correlated with known clinical and pathological prognostic factors, such as HPV status and LRIG1, CD44, Ki67, and p53 expression.Results: Our results show that high LMO7 expression is associated with significantly longer overall survival (OS) (p = 0.044). LMO7 was a positive prognostic factor for OS in univariate analysis (HR 0.515, 95% CI: 0.267–0.994, p = 0.048) but not in multivariate analysis. The LMO7 expression correlated with LRIG1 expression (p = 0.048), consistent with previous findings. Interestingly, strong LRIG1 staining intensity was an independent negative prognostic factor in the HPV-driven group of tumors (HR 2.847, 95% Cl: 1.036–7.825, p = 0.043).Conclusions: We show for the first time that high LMO7 expression is a positive prognostic factor in OPSCC, and we propose that LMO7 should be further explored as a biomarker. In contrast to previous reports, LRIG1 expression was shown to be an independent negative prognostic factor in HPV-driven OPSCC.
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| 6. |
- Kacperczyk-Bartnik, Joanna, et al.
(författare)
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Clinician attitude towards sexual counseling in women with gynecologic malignancies : European Network of Young Gynaecological Oncologists (ENYGO) survey
- 2022
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Ingår i: International Journal of Gynecological Cancer. - : BMJ Publishing Group Ltd. - 1048-891X .- 1525-1438. ; 32:10, s. 1309-1315
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Both the location of primary disease and treatment side effects may have an impact on sexual function in oncogynecological patients. The aim of this study was to examine the prevalence, strategies, difficulties, and ideas for improvement in sexual counseling among specialists managing patients with gynecologic malignancies.METHODS: This was a cross-sectional survey study performed among healthcare professionals treating patients with gynecologic malignancies. A self-prepared questionnaire included 61 questions concerning general demographic information and different aspects of sexual counseling in the gynecologic oncology practice. Analysis included attitudes, behaviors, management strategies, difficulties, and ideas for possible systemic improvements. Statistical analysis involved descriptive statistics, two-sided chi-square test, and Fisher's exact test.RESULTS: A total of 150 respondents from 46 countries answered the survey. The majority of survey participants stated that sexual counseling of oncological patients is very important (n=73, 49%) or important (n=46, 31%). One hundred and two (68%) respondents agreed that sexual counseling of gynecologic oncology patients should be routinely provided by the specialist managing the primary disease. However, collecting information concerning sexual function is performed often or always by only 21% of respondents and 19% discuss the topic rarely or never. The most frequently indicated barriers leading to difficulties in sexual counseling include lack of time (74%), lack of specialist knowledge (55%), and patient embarrassment (48%). One hundred and seven (71%) respondents expressed interest in participating in sexual counseling workshops organized by the European Society of Gynaecological Oncology (ESGO)/European Network of Young Gynaecological Oncologists (ENYGO), 74 (49%) would like to access webinars on the topic, and 120 (80%) would be interested in materials in the ESGO online educational resources.CONCLUSION: One of the proposed solutions to insufficient access to sexual care for women with gynecologic malignancies is providing access to specialist educational programs for both patients and healthcare specialists.
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| 7. |
- Lorenzzi Löfgren de Melo, Alexandra, et al.
(författare)
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Single-molecule array assay reveals the prognostic impact of plasma LRIG1 in ovarian carcinoma
- 2022
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 61:11, s. 1425-1433
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ovarian carcinoma is the eighth most common cause of cancer death in women worldwide. The disease is predominantly diagnosed at a late stage. This contributes to high recurrence rates, eventually leading to the development of treatment-resistant disease. Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is a transmembrane protein that functions as a tumor suppressor and regulator of growth factor signaling. LRIG1 levels have not been investigated in human plasma previously.Materials and methods: A quantitative LRIG1-specific single molecule array assay was developed and validated. LRIG1 levels were quantified in plasma samples from 486 patients with suspicious ovarian masses.Results: Among women with ovarian carcinoma, LRIG1 levels were significantly elevated compared to women with benign or borderline type tumors. High LRIG1 plasma levels were associated with worse overall survival and shorter disease-free survival both in the group of all malignant cases and among the stage 3 cases only. LRIG1 was an independent prognostic factor in patients with stage 3 ovarian carcinoma.Conclusion: LRIG1 plasma levels were elevated in patients with ovarian carcinoma, and high levels were associated with poor prognosis, suggesting that LRIG1 might be an etiologic factor and a potentially useful biomarker in ovarian carcinoma.
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| 9. |
- Patthey, Annika, et al.
(författare)
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Combination of aneuploidy and high S-phase fraction indicates increased risk of relapse in stage I endometrioid endometrial carcinoma
- 2021
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Ingår i: Acta Oncologica. - : Taylor & Francis Group. - 0284-186X .- 1651-226X. ; 60:9, s. 1218-1224
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Endometrioid endometrial carcinoma is a cancer type with generally excellent prognosis when diagnosed at an early stage, but there is a subset of patients with relapsing disease in spite of early diagnosis and surgical treatment. There is a need to find prognostic markers to identify these patients with increased risk of relapse. Depth of myometrial invasion, histological grade, and presence of lymphovascular invasion are known risk factors. DNA content (ploidy) and proliferation measured as S-phase fraction (SPF) have been discussed as prognostic markers but need additional evaluation.MATERIAL AND METHODS: We evaluated relapse-free survival (RFS) with respect to ploidy and SPF, which was analyzed by flow cytometry on fresh tumor tissue, in a cohort of 1001 women treated for stage I endometrioid endometrial carcinoma in northern Sweden during the period of 1993-2010, with a median follow up time of 12.0 years. Data were obtained from historical records.RESULTS: In simple analysis, both aneuploidy and high SPF were associated to increased risk of relapse with hazard ratios (HR) 2.37 (95% CI 1.52-3.70) and 1.94 (95% CI 1.24-3.02), respectively. Our data also confirmed stage, tumor grade, and ploidy as independent prognostic markers in an age adjusted cox regression multivariable analysis but we did not find SPF to contribute to prognosis. However, the combination of aneuploidy and high SPF identified a group of patients with increased risk of relapse, HR 2.02 (95% CI 1.19-3.44).CONCLUSION: In this study, which is the largest study of ploidy and SPF in stage I endometrioid endometrial carcinoma using fresh frozen tissue, aneuploidy was shown to be an independent prognostic marker. Furthermore, the combination of aneuploidy and high SPF could be used to identify patients with increased risk of relapse.
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