The frequency and prognostic role of P53 and P16 immunoexpression in primary ovarian mucinous tumors.

BACKGROUND: Primary ovarian mucinous tumors are uncommon. Factors leading to invasive progression and metastatic disease have not been fully delineated yet. The aim of this study is to determine the rates of p53 and p16 immunoexpressions in primary ovarian mucinous tumors, to investigate their relationship with clinicopathologic factors and their impact on prognosis and survival. METHODS: Seventy-eight primary ovarian mucinous tumors (30 mucinous cystadenomas, 30 mucinous borderline tumors (MBOT), 18 mucinous carcinomas (MOC)) were evaluated immunohistochemically with p53 and p16 staining. The demographic, clinicopathological data, and postoperative follow-up findings of the patients were analyzed. RESULTS: Mutation-type p53 staining was present in 1/30 (3.3 %) cystadenoma, 10/30 (33.3 %) MBOT and 9/18 (50 %) MOC (p = 0.001). p16 overexpression was detected in 3/30 (10.0 %) MBOT and 5/18 (27.8 %) MOC, but not in any cystadenoma (p = 0.04). The frequency of mutation-type p53 staining in MBOTs with microinvasion was higher (71.4 %) than in those without (28.6 %, p = 0.026). The frequencies of p16 or p53 mutations were similar in MBOTs with and without intraepithelial carcinoma, or mural nodule (p > 0.05). In MOCs with ovarian surface involvement, mutation-type p53 staining was detected in 66.7 % (6/9) and p16 overexpression in 55.6 % (5/9) of the cases. A significant difference was found between MOCs with or without ovarian surface involvement regarding the frequency of p16 overexpression (p = 0.029). Any relationship was not detected between survival and p53 and p16 expression in MOCs (p > 0.05). CONCLUSION: p53 and p16 mutation rates were higher in MOCs compared to mucinous cystadenomas and MBOTs and suggest a relevant role in the development of primary ovarian mucinous carcinoma, however further studies are needed in this regard.

The role of HPV in the etiopathogenesis of pterygium and the relationship with recurrence.

PURPOSE: The primary aim of this study was to determine the prevalence of HPV in pterygium with polymerase chain reaction (PCR) testing and to investigate the relationship with clinicopathological factors. A secondary aim was to evaluate the relationship between HPV and the recurrence of pterygium. METHODS: The study included 60 patients. PCR analysis was used to determine the presence of HPV. All the patients were followed up in respect of the development of recurrence. Analyses were performed of patient age, pterygium site, specimen and pterygium size, histopathological findings, HPV status, operation technique and postoperative follow-up findings. In the HPV-positive patients, the relationship between HPV subtypes and other factors was evaluated. To determine the risk factors affecting recurrence rates, multivariate Cox regression analysis was applied subsequent to univariate analysis. In the Cox regression model, HPV status, age, sex, specimen size, size and site of pterygium were included among factors that may affect recurrences rates. RESULTS: Of the total 60 patients, the HPV-PCR test result could not be analysed in 14 because of an insufficient sample. Of the 46 patients with sufficient material for HPV-PCR analysis, the HPV-PCR result was positive in 15 (32.6%). The HPV subtype most often determined was type 16. No statistically significant relationship was determined between HPV positivity and HPV subtype and age or sex. Recurrence was determined in 10% of all the patients. Of the cases determined with recurrence, 66.7% were HPV positive. According to Kaplan-Meier analysis, the recurrence rates in HPV-positive and HPV-negative patients were 26.7% and 6.5%, respectively. A statistically significant difference was found between two groups in terms of recurrence rates (p: 0.046). According to the results of multivariate Cox regression analysis, though not statistically significant, the risk of recurrence was increased 6.18 times in HPV-positive patients with pterygium compared to HPV-negative ones. CONCLUSION: HPV infection may have a role in the development of pterygium and recurrence, but may not be sufficient alone. HPV probably has a role in the development of pterygium by acting together with several co-factors in the multi-stage process.

Rate of Incidental Pathological Lesions in Reduction Mammoplasty Specimens and Incidence of Invasive Breast Carcinoma Following Breast Reduction Operation.

INTRODUCTION: Reduction mammoplasty (RM) is one of the most frequently performed surgical procedures. The incidental determination of significant pathologic lesions (SPL), that is precursor and malignant lesions, in RM specimens is rare. The aim of this study was to determine the frequency of SPL in RM specimens, to evaluate the relationship between SPL and clinicopathological factors, and to examine the incidence of invasive breast carcinoma forming in the remaining breast tissue during the postoperative follow-up period developing in patients after RM operation. MATERIAL AND METHOD: This retrospective study included 874 females who underwent RM operation between January 2012 and January 2021. Demographic, clinicopathological findings, and preoperative radiological findings were recorded. The patients were followed up after the RM operation in respect of the first occurrence of breast cancer. RESULTS: Invasive carcinoma was determined in 0.2% and SPL in 3.5% in RM. The probability of SPL determination was greater in patients aged ≥ 40 years and with ≥ 4 paraffin blocks (p=0.038, p=0.01, respectively). No statistically significant difference was found between patients with and without SPL in respect of radiological findings (p=0.35). The mean postoperative follow-up period was 53.6 months, and invasive carcinoma was diagnosed during follow-up in 0.2% of all patients (6.9% of the patients with SPL). CONCLUSION: Age over 40 years and an increased number of sampled blocks were found to be factors increasing the possibility of the determination of precursor and malignant lesions in RM specimens. RM could decrease the risk of the development of breast cancer. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Concordance of HER2 status tested by IHC and FISH in biopsy and surgical resection specimens and comparison with clinicopathological features in gastric carcinoma.

Context: HER2-targeted therapy has been shown to benefit HER2-positive gastric cancer. It is very important to determine the HER2 expression level correctly to select the appropriate test and sampling method. Aim: In this study, we investigated the frequency of overexpression of HER2 and intratumoral heterogeneity of HER2-positive cases, comparison of HER2 used immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) performance in biopsy and resection specimens, the correlation of HER2 status between biopsy and resection specimens, and its relationship with clinicopathological findings. Materials and Methods: Formalin-fixed, paraffin-embedded specimens of a total of 40 surgically resected and biopsy specimens of gastric cancer were analyzed. HER2 status was examined using both IHC and FISH techniques, and the findings and their association with different clinicopathological parameters were evaluated. Results: The concordance rate between the results of IHC and FISH in biopsy and resection specimens was 96.6% and 86.6%, respectively. In paired 20 cases, the overall concordance rate of HER2-IHC and HER2-FISH status between biopsy and resection specimens was 90% and 100%, respectively. HER2-IHC analysis revealed that 5/40 cases were IHC 2+ and only 1 of 5 IHC 2+ cases demonstrated HER2-FISH amplification. Conclusion: Our results showed that HER2-IHC was well concordant with FISH in cases with a score of 0/1+ or 3+ and demonstrates strong concordance between biopsy and resection specimens. FISH should be performed when the IHC result is equivocal. In our study, no statistically significant correlation was observed between HER2 positivity and clinicopathological parameters. Overall, both biopsy and resection specimens are appropriate for HER2 testing.

Expression of p16 in pterygium and its relation with epithelial dysplasia and possible etiologic role of HPV.

Context: p16 is an important tumor suppressor gene and responsible for regulating the cell cycle. Diffuse positivity with p16 in the cervix and head/neck carcinomas can be regarded as a surrogate marker of the presence of high-risk human papillomavirus (HPV). Aim: The aim of our study was to search the existence of p16 expression in pterygium. We also analyzed the association of p16 expression with epithelial dysplasia and HPV expression. Subjects and Methods: The study enrolled 75 cases of pterygium. The conjunctival tissues of 10 patients excised by the strabismus surgery were used as control group. All of the slides were stained with p16 via the immunohistochemical method. Results: 49 (65%) of pterygiums showed low-grade epithelial dysplasia. None of the control groups showed dysplasia. Positive expression of p16 in patient group was significantly higher (P < 0.001). Staining percentage (SP) of p16 was between 0 and 26% in pterygium; mean SP was 5.1%. There was no staining in the control group. A total of 59 (72%) pterygium cases were positive with p16. Appoximately 42 of 49 (85%) cases with dysplasia showed p16 staining. There was a significant relation between dysplasia and positive expression of p16 (P < 0.001). Conclusions: P16 is significantly expressed in pterygium and correlated with epithelial dysplasia. Furthermore, the existence of p16 expression suggests that HPV is a possible ethiological factor in pterygium. We think that examination of p16 expression and analysis of HPV DNA in p16 positive cases can help us to understand the etiopathogenesis of the disease better.

FOXA1 is associated with high tumor grade, myometrial invasion and lymph node invasion in endometrial endometrioid carcinoma.

OBJECTIVES: FOXA1 expression has been demonstrated in several hormone-dependent cancers. However, data are limited concerning the role of FOXA1 in endometrial cancers. The present study aimed to investigate FOXA1 expression via the microarray technique in benign hyperplasia, endometrial intraepithelial neoplasia, and endometrial endometrioid carcinoma. We also aimed to determine whether there were any associations between FOXA1 expression, tumor grade, myometrial invasion and lymphatic invasion. MATERIAL AND METHODS: Paraffin-embedded sections prepared from samples obtained from 114 patients who underwent surgical hysterectomy or curettage were analyzed. Data were retrieved from digitally-stored medical records. Tissue microarrays were prepared from formalin-fixed, paraffin-embedded tissue blocks. Full tumor sections were used for immunohistochemical analysis performed. RESULTS: Carcinomas with nuclear grade 3 had higher FOXA1 values than others, while grade 2 carcinomas also had higher FOXA1 values relative to grade 1 (p < 0.001). FOXA1 values of FIGO stage III carcinomas were significantly higher than others and stage II values were also significantly higher than stage I FOXA1 values (p < 0.001). Patients with myometrial and lymph node invasion had significantly higher FOXA1 values than others (p < 0.001 and p = 0.047, respectively). FOXA1 had 91.30% sensitivity, 63.60% specificity and 77.78% accuracy for predicting the presence of myometrial invasion with a cut-off value of 9. CONCLUSIONS: FOXA1 expression is higher in endometrial endometrioid carcinoma compared to benign endometrial hyperplasia or intraepithelial neoplasia. In patients with endometrial endometrioid carcinoma, high FOXA1 expression is associated with high tumor grade, myometrial and lymph node invasion. However, FOXA1 expression is not associated with lymphovascular or cervical invasion.

The role of cyclin D1, BCL-2, p53 and Ki-67 in epithelial cells in the etiopathogenesis of pterygium.

CONTEXT: Pterygium is a degenerative disease that consists of conjunctival epithelia and fibrovascular tissue. Some studies suggest that there is a defect in the regulation of apoptosis in the epithelial cell cycle characterized by the development of the disease. But, still this matter being debated. AIMS: In this study, the clinical, histopathological data, and the expression of the cell cycle regulator Cyclin D1, anti-apoptotic BCL-2, tumor suppressor p53, and cell proliferation marker Ki-67 were searched in pterygium samples. SUBJECTS AND METHODS: The study enrolled 62 cases of primary pterygium who underwent excision between 2014 and 2017. Recurrent and pseudo-pterygium cases were excluded from series. The clinical data were obtained from the patient files and the slides were reevaluated for the histopathological data. Slides of all were stained by Cyclin D1, BCL-2, and Ki-67 by the immunohistochemical method. For each immunohistochemical marker, first the staining was determined as negative or positive. Then if there is a staining, the hot zone (the area containing more positive cells) was determined and staining percentage (SP) was assessed by counting positive cells/100 epithelial cells). RESULTS: Solar elastosis, edema, inflammation, and epithelial dysplasia were found statistically different between the control group and the patient group (P value <0.001, <0.001, <0.001 <0.001, respectively). A significant difference was found for staining percentage (SP) of Ki-67, p53, BCL-2 between the control group and the patient group (P values <0.001, 0.002, <0.001, respectively). There were no significant differences in the SP of Cyclin D1 between the two groups (p: 0,133). CONCLUSIONS: Our results indicate an abnormal expression of p53, BCL-2 and elevated proliferation measured by Ki-67 in pterygium samples when compared to normal conjunctiva. Besides the mesenchymal changes, the increased proliferation and the failure of apoptosis in the epithelial cells participate in the development of pterygium, as well.

The extent of cyclin D1 expression in endometrial pathologies and relevance of cyclin D1 with the clinicopathological features of endometrioid endometrial carcinoma.

BACKGROUND: Cyclin D1, a member of the cyclin protein family, is instrumental in the cell cycle due to its influence on the progression from G1 to the S phase. Its overexpression causes reduced doubling time and is also associated with clonogenic growth. The purpose of the present study was to assess cyclin D1 expression in patients with simple hyperplasia (SH), endometrial intraepithelial neoplasia (EIN) and endometrioid endometrial carcinoma, and to evaluate whether there was an association between cyclin D1 expression and the clinicopathological features of endometrioid endometrial carcinoma. METHODS: Retrospective data were available for 193 patients (30 SH, 40 EIN, and 123 endometrioid endometrial carcinoma cases). To detect cyclin D1 expression, immunohistochemistry staining was performed with tissue microarrays. RESULTS: The percentage of cases with positive cyclin D1 staining were 30%, 60% and 78%, for SH, EIN and endometrioid endometrial carcinoma, respectively (P < 0.001). Carcinomas with higher nuclear grade, histological grade, and FIGO grade displayed higher mean cyclin D1 expression compared to lower grade carcinomas. In addition, patients with lymphovascular invasion (P = 0.006), myometrial invasion (P < 0.001) and lymph node invasion (P < 0.001) had higher mean cyclin D1 expression compared to those without invasion. There was a significant correlation between cyclin D1 expression and clinicopathological features of endometrioid endometrial carcinoma including tumor grade, FIGO grade, lymphovascular invasion, lymph node invasion and myometrial invasion (P < 0.05 for each). CONCLUSION: Cyclin D1 expression is significantly higher in patients with endometrioid endometrial carcinoma compared to that of the SH and EIN. The extent of cyclin D1 expression is strongly correlated with nuclear and histological grade, myometrial invasion, lymphovascular invasion and lymph node invasion in patients with endometrioid endometrial carcinoma. These findings contribute in several ways to our understanding of cyclin D1 expression and provide a basis for future research on this topic.

The diagnostic significance of trophoblast cell-surface antigen-2 expression in benign and malignant thyroid lesions.

CONTEXT: Thyroid cancers are the most common malignancy of the endocrine system. Over-expression of trophoblast cell-surface antigen 2 (TROP-2) in various tumors has been found to correlate with poor prognosis and aggressive tumor behavior. AIMS: The aim of this study was to evaluateTROP-2 expression in thyroid neoplasms. SUBJECTS AND METHODS: This study contained 152 cases, including 48 follicular nodular disease (FND), 29 follicular adenoma (FA), 57 papillary thyroid carcinoma (PTC), 12 follicular thyroid carcinoma (FTC), 3 medullary thyroid carcinoma (MTC), 2 poorly differentiated thyroid carcinoma (PDTC) and 1 undifferentiated thyroid carcinoma (UDTC). TROP-2 expression was investigated via immunohistochemistry in sections prepared from paraffin blocks of the cases. RESULTS: The cases comprised 32 (21%) males and 120 (79%) females with a mean age of 46.8 years (range, 15-85 years). TROP-2 expression was observed in 74.6% of the malignant lesions of the thyroid except for medullary carcinoma, poorly differentiated and undifferentiated thyroid carcinoma. Immunoreactivity was 3.4% in FA, 41.7% of cases with FTC and 81.8% in PTC follicular variant (PTC fv). The difference between FA/FTC and FA/PTC follicular variant were both significant (P < 0.005, P < 0.001, respectively). There was no difference between FTC/PTC fv (P = 0.089). CONCLUSION: TROP-2 can be considered a useful marker for distinguishing PTC fv cases from follicular nodular disease and follicular adenoma cases because of its high sensitivity in the identification of papillary carcinomas of the thyroid.

The risk of malignancy according to Milan reporting system of salivary gland fine-needle aspiration with Becton Dickinson SurePath liquid-based processing.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is a noninvasive, safe, cost-effective, diagnostic procedure for the evaluation of salivary gland lesions and the selection of patients for surgery. The aim of this study was to analyze the risk of malignancy (ROM) according to the Milan reporting system of salivary gland FNA specimens using a liquid-based cytology (LBC) technique. METHODS: The cytological diagnosis of 459 cases between 2014 and 2017 was revised according to the Milan reporting system. The FNAC results of 129 cases with a histological diagnosis were compared with respect to the final diagnosis. The ROM for each category calculated. RESULTS: The ROM was high in the indeterminate and malignant categories, while the ROM in the benign neoplasm category was low. Sensitivity and specificity analyzed in two different ways were 95.1% and 88.8%, 81%, and 77.7%, respectively. CONCLUSIONS: When salivary gland lesions are evaluated together with clinical and radiological data, the LBC technique can be applied to salivary gland specimens based on the high diagnostic sensitivity and specificity in liquid-based samples reported according to the Milan system.