Gozde Kir

Correlation of PD-L1 expression with immunohistochemically determined molecular profile in endometrial carcinomas

Endometrial carcinoma programmed death-ligand 1 (PD-L1) expression in tumor cells (TCs) and tumor-associated inflammatory cells (ICs) have recently been reported in several studies which vary in terms of their cohort size, design, and methodology. We aimed to assess PD-L1 staining in endometrial carcinomas and correlate this with clinical and pathological factors and PTEN, ARID1A, p53, and MMR protein expression. PD-L1 immunohistochemistry was performed on whole tissue sections of all tumor blocks of 59 consecutive unselected endometrial carcinomas between November 2018 and September 2019. TC and IC PD-L1 positivity with a 1% cut-off value was observed in 10.2% and 67.8% of cases, respectively, and with a 5% cut-off value in 3.4% and 42.4% of cases, respectively. TC PD-L1 positivity with both 1% and 5% cut-off values was significantly related to ARID1A loss (p = 0.001 and p = 0.046, respectively). IC PD-L1 positivity with 1% and 5% cut-off values and combined score were significantly associated with MMR protein deficiency (p = 0.041, p = 0.031, and p = 0.028, respectively). Advanced stage tumors exhibited more frequent PD-L1 expression in ICs (p = 0.039). MELF-type myometrial invasion pattern was more common in tumors with ARID1A loss (p = 0.047). We observed higher rates of IC PD-L1 positivity in endometrial carcinomas than documented in prior studies; this may be related to our usage of "recent" paraffin blocks and whole tissue sections of all tumor blocks. There was a much higher PD-L1 expression in the ICs compared to TCs in our cases. We confirm a previously documented association between MMR deficiency and PD-L1 expression and show a novel association between ARID1A loss and PD-L1 expression in endometrial carcinomas. ARID1A loss represents a potential biomarker of immune checkpoint inhibitor response in endometrial carcinoma.

HPV-independent squamous sell carcinoma of cervix: a clinicopathological, immunohistochemical, and molecular analysis of six cases

Abstract HPV-independent squamous cell carcinoma (SCC) of the cervix is a rare subtype associated with aggressive clinical behavior and poor prognosis, as reported in limited studies with small sample sizes. This study aims to investigate the clinicopathological, immunohistochemical, and molecular characteristics of six cases of HPV-independent SCC. Formalin-fixed, paraffin-embedded tissues from six patients were analyzed using immunohistochemistry and Next-Generation Sequencing (NGS). Human papillomavirus (HPV) testing was performed using the Aptima HPV assay, and immunohistochemical markers, including p16, p53, PD-L1, HER2 and CK5/6 were evaluated. The median age at diagnosis was 62 years. Key histopathological features included an infiltrative-destructive growth pattern, pronounced keratinization, and extensive necrosis in the majority of cases. All tumors were p16-negative and high-risk HPV-negative by the Aptima HPV assay, confirming their HPV-independent status. One case exhibited p53 overexpression and HER2 positivity (score 3 +). Five out of six patients succumbed to the disease. FIGO stages ranged from IIB to IVB. Molecular analysis identified mutations in TP53 and PIK3CA, as well as novel CTNNB1 and TERT promoter mutations, and HER2 amplification . In five of six patients PD-L1 expression with at least CPS score of 2,5 was observed. HPV-independent cervical SCC typically affects older patients and is associated with poor clinical outcomes. This study highlights TP53 and PIK3CA mutations and novel findings, including CTNNB1, TERT promoter mutations, and HER2 amplification. The observed PD-L1 expression patterns may suggest potential benefits from immunotherapy. Further research is warranted to better understand the clinicopathologic characteristics and molecular drivers of HPV-independent SCC and to explore novel therapeutic strategies.

High-risk human papillomavirus (HPV) detection in formalin-fixed paraffin-embedded cervical tissues: performances of Aptima HPV assay and Beckton Dickinson (BD) Onclarity assay

Aim There are many scenarios where high-risk human papillomavirus (HPV) detection in formalin-fixed paraffin-embedded (FFPE) specimens is important. However, there is no Food and Drug Administration (FDA)-approved and clinically validated technique for detecting high-risk HPV in FFPE tissues. In this study, we evaluated two commercially available HPV assays which are FDA-approved for use on cytology specimens, the Aptima HPV assay and the Beckton Dickinson (BD) Onclarity assay, to detect high-risk HPV in FFPE tissues of cervical high-grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC). Methods A total of 189 cases (46 SCC, 107 HSIL and 36 benign/normal) were tested for high-risk HPV with the Aptima HPV assay and a subset of cases (n=97) with the BD Onclarity assay. Results The sensitivities of the Aptima and BD Onclarity HPV assays were 99.4% (95% CI 96.46% to 99.98%) and 75.9% (95% CI 65.27% to 84.62%), respectively; the specificity and positive predictive value (PPV) of the two assays were 100%. Negative predictive values of the Aptima and BD Onclarity HPV assays were 97.3% (95% CI 83.61% to 99.61%) and 67.7% (95% CI 58.91% to 75.47%), respectively. The kappa value (0.96) for comparison of the distribution of high-risk HPV types between the two assays was high. HPV 16 was the most common high-risk HPV type for HSIL and SCC cases. However, SCC cases had higher percentages of HPV 16 and HPV 18/45 and lower percentages of other high-risk HPV types compared with HSIL cases. Conclusion Both assays are reliable methods for high-risk HPV detection and genotype determination in FFPE specimens, with high PPV and specificity. The Aptima HPV assay has the advantage of higher sensitivity. As far as we are aware, this is the first study comparing the Aptima HPV assay and the BD Onclarity assay in FFPE tissues. Our study results should be tested and confirmed in larger cohorts.

Immediate histopathologic correlation in Turkish population with negative cytology and high‐risk human papillomavirus positivity: A retrospective analysis of high‐risk human papillomavirus genotype and stratified by age

AbstractIntroductionAccording to the American Society of Colposcopy and Cervical Pathology (ASCCP) recommendations, regardless of age, women with high‐risk infections other than human papillomavirus 16/18 positivity (other hrHPV) and negative cytology should not be referred directly to colposcopy. Several studies compared detection rates of ≥high‐grade squamous intraepithelial lesion (HSIL) between HPV 16/18 ± 45, and other hrHPV types on colposcopic biopsy.MethodsWe designed a retrospective study to determine the presence of ≥HSIL in colposcopic biopsy in women with negative cytology and hrHPV positivity during the years 2016–2022.ResultsHPV 16/18/45 had a PPV of 43.8%, while other hrHPV types had a PPV of 29.1% for a tissue diagnosis of ≥HSIL. For a tissue diagnosis of ≥HSIL detection, there was no statistically significant difference between the PPV of other hrHPV and HPV 16/18/45 in patients ≥30. There were only two cases with a tissue diagnosis of ≥HSIL in the other hrHPV group of women under 30 years of age.ConclusionWe suggested that the follow‐up recommendations of ASCCP for patients above the age of 30 with negative cytology and other hrHPV positivity may not be fully applicable to countries like Turkey with a different healthcare environment. Referring to patients ≥30 who had other hrHPV positivity and negative cytology to direct colposcopy may be clinically beneficial, particularly in populations where a colposcopic examination is easy and inexpensive.