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.

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.

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 .

TGF-ß-SMAD-miR-520e axis regulates NSCLC metastasis through a TGFBR2-mediated negative-feedback loop.

Transforming growth factor-ß (TGF-ß) pathway plays crucial roles during the carcinogenesis and metastasis. TGF-ß receptor 2 (TGFBR2) is a key molecule for the regulation of TGF-ß pathway and frequently downregulated or lost in several cancer types including non-small cell lung cancer (NSCLC), and TGF-ß pathway is often regulated by negative-feedback mechanisms, but little is known about the mechanism of TGFBR2 downregulation in NSCLC. Here, we found that the expression of miR-520e is upregulated in metastatic tumor tissues compared with non-metastatic ones, and its expression is inversely correlated with that of TGFBR2 in clinical samples. We also discovered that TGF-ß dramatically increased the expression of miR-520e, which targeted and downregulated TGFBR2, and the suppression of miR-520e significantly impaired TGF-ß-induced TGFBR2 downregulation. Chromatin immunoprecipitation-PCR experiments further showed that miR-520e is transcriptionally induced by SMAD2/3 in response to TGF-ß. Our findings reveal a novel negative-feedback mechanism in TGF-ß signaling and the expression level of miR-520e could be a predictive biomarker for NSCLC metastasis.

HMGB1 expression in urothelial carcinoma of the bladder.

PURPOSE: HMGB1, the most important member of the high mobility group box protein family, is a nuclear protein with different functions in the cell; it has a role in cancer progression, angiogenesis, invasion, and metastasis development. We studied the expression of HMGB1 and whether it is a prognostic factor in urothelial carcinoma of bladder (UCB) or not. METHODS: The study included 90 cases that were histopathologically diagnosed with UCB in the tissue samples obtained by transurethral resection (TUR). HMGB1 expression was investigated by immunohistochemistry. RESULTS: A total of 90 patients, 80 (88.9%) male and 10 (11.1%) female, were enrolled in the study. The histopathological diagnosis was infiltrating urothelial carcinoma (IUC) in 63 (70.0%) and non-invasive papillary urothelial carcinoma (NIPUC) in 27 (30.0%). When the NIPUC cases were grouped according to grade, 24 (88.9%) of the cases were low grade and 3 (11.1%) were high grade. HMGB1 expression was found positive in 51 (56.7%) and negative in 39 (43.3%) of the patients. HMGB1 expression was significantly higher in IUCs (p=0.046). CONCLUSION: The results of our study demonstrate that HMGB1 overexpression has a significant role in UCB progression and it corroborates the idea that it might be an important prognostic factor.

Expression of claudin 1, 4 and 7 in thyroid neoplasms.

The distinction of thyroid carcinoma from benign thyroid neoplasm, as well as the subtyping of papillary carcinoma (PC) and follicular carcinoma (FC), may be performed histopathologically in the majority of cases. However, in certain cases, it is difficult to histopathologically distinguish between PC and FC, as well as follicular adenoma (FA), FC and the dominant nodule of multinodular goiter (MNG-DN). The present study aimed to determine the roles of the expression levels of the tight junction proteins claudin 1, 4 and 7 in the differential diagnosis of PC, FC, FA, MNG-DN, medullary carcinoma (MC) and anaplastic carcinoma (AC). The current study included 114 cases of histopathologically diagnosed thyroid neoplasia, which were distributed as follows: 29 FA, 18 MNG-DN, 47 PC, 10 FC, 5 MC and 5 AC. The expression levels of claudin 1, 4 and 7 were examined using immunohistochemical methods. The results revealed a significant difference in claudin 1 expression between malignant and benign thyroid neoplasms (P<0.001). Claudin 1 expression was not detected in any of the MNG-DN cases, and no significant difference in claudin 1 expression levels was identified between FA and FC (P=0.653). However, a statistically significant difference was observed between FC and PC (P<0.001). Claudin 4 expression did not differ between malignant and benign thyroid neoplasms, neither between MNG-DN, FA and FC, nor between FC and PC (P=0.068, P=0.502 and P=0.481, respectively). Claudin 7 exhibited positive immunohistochemical staining in 107 patients (94%); however, no significant difference in claudin 7 expression §levels was identified between malignant and benign thyroid neoplasms among MNG-DN, FA and FC (malignant, P=0.135; benign, P=0.470). Claudin 7 exhibited positive staining in all PC and FC cases. Therefore, claudin 1 expression levels may be useful in distinguishing cases of FC and PC with overlapping histopathological features, and provide a novel immunohistochemical marker for the subtyping of thyroid carcinoma.

Leptin and leptin receptors in salivary glands of primary Sjögren's syndrome.

BACKGROUND: The role of leptin in primary Sjögren's syndrome (SS) pathogenesis is unknown. The aim of this study was to investigate the expression of leptin and leptin receptor (LEPR) in minor salivary glands in patients with SS. MATERIALS AND METHODS: The expression of leptin and LEPR in minor salivary gland specimens obtained from patients with primary SS (n=50) and control subjects (n=50) were examined using immunohistochemical staining. RESULTS: Acinar cells, epithelial cells and adipocytes in salivary glands can express leptin and LEPR. It was observed that there was intense staining in the focal lymphocytic infiltration areas in SS patients. The intensity of leptin and LEPR staining under microscopy (400×) were graded semiquantitatively as negative, mild, moderate or strongly positive, and scored as 1, 2 or 3, respectively. The expression levels of leptin and LEPR in patients with primary SS were not higher than in controls. There was no significant difference in degrees of leptin and LEPR staining, staining intensity, and immunoreactive scores between groups. The expression of leptin and LEPR were not correlated with autoantibodies such as RF, ANA, anti-Ro, and/or anti-La positivity. CONCLUSIONS: These findings indicate that leptin and its receptors do not play an important role in primary SS pathophysiology.

Chylous ascites after resection of giant adrenocortical carcinoma.

Postoperative chylous ascites (PCA) is a rare clinical state that occurs during abdominal surgery. Despite its rarity, the need to diagnose and treat PCA is increasing in importance with the increased number of wide resections and lymph node dissections being performed and the serious consequences of treatment. Here we describe the PCA complications we observed after resection for treating a case of giant adrenocortical carcinoma and we have the brief review of the PCA complication.

Expression pattern and prognostic significance of claudin 1, 4 and 7 in pancreatic cancer.

BACKGROUND: Tight junctions (TJs) organise paracellular permeability and they have an important role in epithelial and endothelial cell polarity and permanence of barrier function. It has been demonstrated that the Claudin family constitutes an important component of them. In this study, we assessed expression patterns of of Claudin1, 4 and 7 and whether they have any relation with prognosis in patients with pancreatic cancer. MATERIALS AND METHODS: Expression patterns of Claudin 1,4 and 7 were examined by immunohistochemistry in 25 patients with a histopathological diagnosis of pancreatic cancer using a semiquantitative scoring of the extent and intensity of staining. After grouping the staining scores as low (final score 0-2) and high (final score 3-9) the relation between expression of Claudin 1,4 and 7 and survival was evaluated. RESULTS: There was no significant relation between expression of Claudin 1,4 and 7 and gender and stage. No statistically significant relation was found between Claudin 1 and 4 expression and survival whereas a statistically significant relation was found between decrease in Claudin 7 expression and decrease in survival. CONCLUSIONS: Claudins have important functions other than their popular function known as adhesion. Supporting this hypothesis, we found a statistically significant relationship between increased Claudin 7 expression and increased survival time, and this suggests that Claudin 7 may exert different tumorigenic effects in pancreatic cancer other than its well- known adhesion effect.

Expression of Cox-2 and Bcl-2 in Paget's disease of the breast.

BACKGROUND: Paget's disease (PD) is a rare form of intraepithelial adenocarcinoma that involves breast and extramammarian tissues. It is often associated with ductal carcinoma in situ and/or invasive ductal cancer. Molecular pathways that play a role in development of Paget's disease are stil unclear. Expression patterns of Cox-2 and bcl-2 were therefore assessed. MATERIALS AND METHODS: Patients with a histopathological diagnosis of Paget's disease were included in this study. Patient files were analysed retrospectively. RESULTS: Invasive cancer was diagnosed in 35 (76.1%) of the patients, 7 (15.2%) had ductal carcinoma in situ and 4 (8.7%) patients had no associated neoplasm. Twenty four (52.2%) patients showed COX-2 expression in Paget cells whereas no expression was seen in 22 (47.8%) patients. No relation was found between COX-2 expression and the lesion underlying Paget's disease (p=0.518). Bcl-2 expression in Paget cells was found positive in 12 (26.1%) and negative in 27 (58,7%) cases. There was no relation between Bcl-2 expression and the lesion accompanying Paget's disease (p=0.412). No relation was observed between COX-2 expression and Bcl-2 expression (p=0.389). CONCLUSIONS: In breast cancer, COX-2 expression is associated with poor prognostic factors. As COX-2 expression increases the tendency to metastasize also increases. In our study we found a significantly high COX-2 expression in Paget's disease of the breast. We suggest that COX-2 expression and inflammatory processes may play a role in pathogenesis of the Paget's disease of the breast.

Prognostic role of Aurora-A expression in metastatic colorectal cancer patients.

PURPOSE: Aurora kinase family plays an important role in mitosis and cell cycle organization. Aurora-A is an important member of the aurora kinase family and its expression increases the genomic instability and contributes to carcinogenesis. In this study, the prognostic role of Aurora-A expression in colorectal cancer (CRC) was assessed. METHODS: Metastatic CRC patients, whose diagnoses were histopathologically confirmed and who were followed up at the Antalya Education and Research Hospital between 2008 and 2010, were included in the study. Aurora-A expression was assessed with immunohistochemistry. RESULTS: A total of 40 patients were included in the study. Aurora-A expression was determined as positive in 33 (82.5%) patients and as negative in 7 (17.5%). No significant correlation was determined between Aurora-A expression and tumor location, metastatic location and histological subtype (p=0.549, 0.511, and 0.709, respectively). Also, no significant correlation was determined between Aurora-A expression and overall survival (p=0.202). Median survival was 8.7 months (95) confidence interval/CI 6.9-10.4) in patients with negative Aurora-A expression, whereas it was 22.6 months (95% CI 12-33.3) in patients with positive Aurora-A expression (p=0.202). CONCLUSION: Despite the lack of statistical significance, we speculate that Aurora-A overexpression may have a positive effect on the survival of patients. With this regard, there is a need for further comprehensive studies examining the relation and effect of Aurora-A expression on survival and response to treatment.

Loss of tight junction proteins (Claudin 1, 4, and 7) correlates with aggressive behavior in colorectal carcinoma.

BACKGROUND: Tight junction proteins in the cell organize paracellular permeability and they play a critical role in apical cell-to-cell adhesion and epithelial polarity. Claudins are major integral membrane proteins of tight junctions, especially Claudin 1, 4, and 7, which are known as the impermeability Claudins. In this study, we investigated the importance of loss of Claudin 1, 4, and 7 expression, and their relation to tumor progression in colorectal cancer patients. MATERIAL/METHODS: Loss of Claudin 1, 4, and 7 expression was examined by immunohistochemical method in 70 patients diagnosed with colorectal cancer. Cases with loss of Claudin expression in <1/3 of tumor cells were classified as mild loss, whereas cases with loss of Claudin expression ³1/3 of tumor cells were classified as moderate-to-marked loss in order to evaluate the relation between loss of Claudin 1, 4, and 7 expression and clinicopathologic data. RESULTS: The severe suppression of Claudin 1, 4, and 7 expression was found to be significantly related to the depth of tumor invasion, positive regional lymph nodes, histological grade, lymphovascular invasion, perineural invasion, and lymphocytic response. Additionally, severity of loss in Claudin 4 expression was found to have a relation with distant metastasis. CONCLUSIONS: Claudin 1, 4, and 7 are important building blocks of paracellular adhesion molecules. Their decreased expression in colorectal cancer seems to have critical effects on cell proliferation, motility, invasion, and immune response against the tumor.

Lack of relation of AKAP12 with p53 and Bcl-2 in colorectal carcinoma.

BACKGROUND: AKAP12 inhibits oncogenic proliferation, invasion, chemotaxis and neovascularization. Bcl-2 and p53 are two important apoptotic markers that play roles in apoptotic processes. It has been found that AKAP12 blocks the cell cycle and induces apoptosis in fibrosarcoma cells. In our study we assessed the relationship of AKAP12 with apoptotic markers, Bcl-2 and p53. MATERIALS AND METHODS: Our study included 45 cases that were histopathologically diagnosed with colorectal carcinoma from the tissue samples acquired by surgical resection. AKAP 12, Bcl-2, and p53 expression was examined by immunohistochemistry. RESULTS: A total of 45 colorectal adenocarcinoma patients - 17 (37.8%) females and 28 (62.2%) males - were included in this study. AKAP12 expression was found to be negative in 8 patients (17.8%), and positive in 37 patients (82.2%). Bcl-2 was found positive in 6 patients (13.3%) and p53 in 29 patients (55.6%). AKAP12 expression had no significant relation with Bcl-2 and p53 expression (p:0.939, p:0.079, respectively). CONCLUSIONS: Although various studies have pointed to apoptotic activity of AKAP12, the literature is limited regarding relations with p53 or Bcl-2 expression. In the present study, we found no relation in colorectal carcinomas.

The role of high mobility group box 1 (HMGB1) in colorectal cancer.

BACKGROUND: HMGB1, the most important member of the high mobility group box protein family, is a nuclear protein with different functions in the cell; it has a role in cancer progression, angiogenesis, invasion, and metastasis development. We studied the expression of HMGB1 and whether it is a prognostic factor in colorectal carcinoma. MATERIAL AND METHODS: The study included 110 cases that were histopathologically diagnosed with colorectal carcinoma from the tissue samples acquired by surgical resection and biopsy in Antalya Education and Research Hospital between 2008 and 2012. HMGB1 expression was examined via immunohistochemical method. RESULTS: HMGB1 expression was evaluated as negative in 32 (44.4%) of the patients and as positive in 40 (55.6%) patients. There was no relation between the HMGB1 expression and sex, age, tumor invasion depth, and histological type. However, a significant relation was detected between the HMGB1 expression and lymph node status, metastasis status, and stage (p:<0.001, p:<0.001, p:<0.001, respectively). Similar results were obtained for the relations between the HMGB1 and histological grade, perineural invasion, lymphovascular invasion, and lymphocytic response (p<0.001, p<0.001, p<0.001, and p<0.001, respectively). CONCLUSIONS: The results of our study demonstrate that HMGB1 overexpression has a significant role in tumor progression (especially migration of tumor cells) and tumor ability to metastasize in colorectal cancers; thus, it corroborates the idea that it might be an important prognostic factor.

Tumour markers in peritoneal washing fluid - contribution to cytology.

BACKGROUND: Peritoneal washing cytology (PWC) that shows the microscopic intra-peritoneal spread of gynaecologic cancers is not used in staging but is known as prognostic factor and effective in planning the intensity of the therapy. False negative or false positive results clearly affect the ability to make the best decision for therapy. In this study we assessed levels of tumour markers, carcinoembryonic antigen (CEA), cancer antigen 125 (CA-125) and carbohydrate antigen (CA19-9), in peritoneal washing fluid to establish any possible contribution to the peritoneal washing cytology in patients operated for gynaecologic cancer. MATERIALS AND METHODS: Preoperative tumour markers were studied in serum of blood samples obtained from the patients for preoperative evaluation of a gynaecologic operation. In the same group peritoneal tumour markers were studied in the washing fluid obtained for intraoperative cytological evaluation. RESULTS: This study included a total of 94 patients, 62 with malignant and 32 with benign histopathology. The sensitivity of the cytological examination was found to be 21% with a specificity of 100%. When evaluated with CEA the sensitivity of the cytological examination has increased to 37%. CONCLUSIONS: In addition to examination of PWC, the level of CEA, a tumour marker, in peritoneal washing fluid can make a diagnostic contribution. Determining the level of CEA in peritoneal washing fluid will be useful in the management of gynaecologic cancers.