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.

Relation of beclin-1 and bcl-2 expressions with pathological parameters and prognosis in clear cell renal cell carcinomas.

INTRODUCTION: The most common type of renal cancers is the clear cell renal cell carcinoma (CCRCC) and 98% of CCRCCs have a loss of sequence in the short arm of chromosome 3 by deletion or translocation. Programmed cell death; another possible mechanism of tumorigenesis, comprises two separate components: apoptosis and autophagy. This study aims to show the rela-tion between the prognostic parameters and survival, and Beclin-1, as the representative marker of autophagy, and Bcl-2 as the representative marker of apoptosis in CCRCC patients. In this study, we aimed to determine if Beclin-1 and Bcl-2 expression levels can provide any prognostic information about CCRCC patients. METHODS: We examined a total of 84 patients who underwent partial or radical nephrectomy and were diagnosed as having CCRCC between January 2008 and December 2015. Immunohistochemical staining was performed, the evaluation was for Beclin-1 and Bcl-2 semi-quantitative, and based on the percentage of positively stained cells (proportion) and staining intensity. RESULTS: There was only a statistical significance between Beclin-1 expression and age (r:-0.274; p=0.012; p <0.05). There was a marginal significance between ISUP grade and Beclin-1 (p=0.051). The relation of Bcl-2 expression with the ISUP grade, recurrence, metastasis, and mortality revealed statistical significance (p=0.001, p=0.019, p=0.009, p=0.013, respectively). The ISUP grade and the Bcl-2 expression revealed statistical significance on multivariate analysis ( HR 7.453, 95% CI: 1.935-28.713, p=0.004). The 5-year and 10-year tumor recurrences rates were lower in Bcl-2 positive group, and Bcl-2 positive group experi-enced longer disease free and overall survival. CONCLUSION: There was only marginal correlation between Beclin-1 expression and ISUP grade. No other histopathologic prog-nostic parameters histologic parameters revealed any signigificance. The higher expression of Bcl-2 is correlated with nuclear lower ISUP grade, lower pT stage, and longer disease free and overall survival.

Relation of beclin-1 and bcl-2 expressions with pathological parameters and prognosis in clear cell renal cell carcinomas

Introduction: The most common type of renal cancers is the clear cell renal cell carcinoma (CCRCC) and 98% of CCRCCshave a loss of sequence in the short arm of chromosome 3 by deletion or translocation. Programmed cell death; another possiblemechanism of tumorigenesis, comprises two separate components: apoptosis and autophagy. This study aims to show the relation between the prognostic parameters and survival, and Beclin-1, as the representative marker of autophagy, and Bcl-2 as therepresentative marker of apoptosis in CCRCC patients. In this study, we aimed to determine if Beclin-1 and Bcl-2 expressionlevels can provide any prognostic information about CCRCC patients.Methods: We examined a total of 84 patients who underwent partial or radical nephrectomy and were diagnosed as havingCCRCC between January 2008 and December 2015. Immunohistochemical staining was performed, the evaluation was forBeclin-1 and Bcl-2 semi-quantitative, and based on the percentage of positively stained cells (proportion) and staining intensity.Results: There was only a statistical significance between Beclin-1 expression and age (r:-0.274; p=0.012; p <0.05). There wasa marginal significance between ISUP grade and Beclin-1 (p=0.051). The relation of Bcl-2 expression with the ISUP grade,recurrence, metastasis, and mortality revealed statistical significance (p=0.001, p=0.019, p=0.009, p=0.013, respectively). TheISUP grade and the Bcl-2 expression revealed statistical significance on multivariate analysis ( HR 7.453, 95% CI: 1.935-28.713,p=0.004). The 5-year and 10-year tumor recurrences rates were lower in Bcl-2 positive group, and Bcl-2 positive group experienced longer disease free and overall survival...(AU)

PTEN Loss and PD-L1 Expression of Different Histological Patterns of Prostate Cancer.

AIMS: Although several studies have evaluated PTEN loss in Prostatic Adenocarcinoma (PCa), PTEN loss correlation with different histological patterns only has a few studies. Although several studies have evaluated PD-L1 expression in PCa and its correlation with Gleason scores, as far as we know, there are no prior studies that have included a comparison between PD-L1 expression and histological patterns of PCa. This study aims to evaluate PTEN loss and PD-L1 expression by immunohistochemistry in different histological patterns of PCa. METHODS: The current study included consecutive 98 radical prostatectomy specimens with 151 foci with different Gleason Grade (GG) patterns. RESULTS: The highest frequency of PTEN loss was observed in GG4 cribriform and glomeruloid patterns (59.3%, p < 0.001). Combined score (CS) PD-L1 positivity was observed in fourteen patients (14.2%). Tumor cell (TC) and tumor-associated inflammatory cells (IC) PD-L1 positivity was observed in 10 (10.2%) and 7 (7.1%) patients. The highest frequency of PD-L1 expression was observed in the GG5 pattern, and between GG4 patterns, the irregular pattern had the highest PD-L1 positivity. CONCLUSIONS: In conclusion, in our cohort of consecutive unselected cases of prostatic carcinoma, we observed the highest PTEN loss rate in the GG4 cribriform and glomeruloid pattern and the highest PD-L1 expression rate in the GG5 and GG4 irregular patterns. These results may predict molecular differences between different histological patterns in PCa and may be used to inform a treatment decision. Future studies should investigate these differences between histological patterns of PCa to predict response to immunotherapy in larger cohorts.

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.

Determining the cut-off values of tumor diameter, degree of extraprostatic extension, and extent of surgical margin positivity with regard to biochemical recurrence of prostate cancer after radical prostatectomy.

BACKGROUND: The pre-biopsy (bx) prostate-specific antigen (PSA) level, tumor volume/diameter, degree of extraprostatic extension (EPE), and extent of surgical margin positivity have been shown to be significant prognostic parameters of biochemical recurrence (BCR) after radical prostatectomy. The present study assessed the cut-off values of the pre-bx PSA level, maximum tumor diameter, radial and circumferential distances of EPE, and circumferential length of surgical margin (SM) positivity with regard to BCR. MATERIAL AND METHODS: The study included 445 radical prostatectomy specimens, and the cut-off values of all parameters were determined using receiver operating characteristic curve analysis. RESULTS: An ISUP grade group ≥ 3, radial distance of EPE >1 mm, and circumferential length of SM positivity ≥2 mm were identified as independent predictors of BCR after radical prostatectomy. The parameters that showed statistical significance in univariate analysis, such as pre-bx PSA level ≥ 7.20 ng/mL, tumor diameter ≥ 19.5 mm, presence of seminal vesicle invasion, and circumferential distance of EPE >3 mm, did not have independent prognostic values for BCR. CONCLUSIONS: An ISUP grade group ≥ 3, radial distance of EPE >1 mm, and circumferential length of SM positivity ≥2 mm are predictors of BCR. Our findings might have significance in risk classification and adjuvant therapy consideration among patients with localized prostate cancer.