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.

Histopathological changes in tissues surrounding vagal nerve stimulation generators: A retrospective analysis of revision surgeries.

PURPOSE: Vagal nerve stimulation (VNS) is an effective treatment for patients with epilepsy, depression, and other neuropsychiatric conditions. Understanding the tissue changes associated with VNS devices is crucial for optimizing patient outcomes and device development. This study aimed to investigate the histopathological changes in the tissues surrounding the VNS generator and explore potential correlations with clinical factors and battery performance. METHODS: A total of 23 patients who underwent VNS generator revision surgery owing to battery depletion were included. Tissue samples from the areas surrounding the VNS generator were obtained and analyzed for histopathological changes. Demographic and device-related variables were also recorded. RESULTS: Capsule formation was observed in all patients. Acute inflammation were not detected in any case. Perivascular lymphocytic infiltration, foreign-body giant cell reaction (FBGCR), and calcification were observed in 8.7%, 26.1%, and 43.5% of patients, respectively. Crystalloid foreign body appearance was noted in 4 patients. The median output current of the generator was higher in patients with lymphocytic infiltration than in those without lymphocytic infiltration. The median off time was higher in patients with skin retraction than in those without skin retraction. Moreover, discomfort was associated with the presence of FBGCR. CONCLUSION: Our study provides insights into the tissue changes associated with the VNS generator, with capsule formation being a common response. Crystalloid foreign body appearance was not reported previously. Further research is needed to understand the relationship between these tissue changes and VNS device performance, including the potential impact on battery life. These findings may contribute to VNS therapy optimization and device development.

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 .

Expression of human telomerase reverse transcriptase (hTERT) in thyroid neoplasms.

PURPOSE: Distinction of thyroid neoplasms that include papillary carcinoma (PC) and follicular carcinoma (FC) from benign thyroid neoplasms can be performed successfully by histopathologic examination in most of the cases. However, in some cases it may be difficult to distinct PC and FC as well as FC and follicular adenoma (FA) and also FA and the dominant nodule of multinodular goiter (MNG) histopathologically. In this study, we aimed to determine the role of expression of the human telomerase reverse transcriptase (hTERT) in the distinction of thyroid neoplasms and its relation with prognostic factors by immunohistochemical methods. METHODS: This retrospective study included 138 cases histopathologically diagnosed with benign and malignant thyroid neoplasia. Sections obtained from formalin-fixed paraffin- embedded blocks were stained with hTERT antibody. Cases were divided into hTERT-positive and -negative categories according to hTERT expression score that included percentage and intensity of staining in neoplastic cells. RESULTS: hTERT expression was negative in 93 (67.4%) and positive in 45 (32.6%) patients. Twenty-three (46.0%) of 50 PC, 12 (36.0%) of 33 FA, 1 (10.0%) of 10 FC, 4 (13.0%) of 31 MNG, 2 (66.0%) of 3 medullary carcinoma (MC) patients were found hTERT (+), showing that the difference between PC and FC was significant (p=0.034). There was also a significant difference between FA and MNG (p=0.030). There was no difference between FA and FC (p=0.117). CONCLUSION: The high expression of hTERT can be useful for making a differential diagnosis between PC and FC, and between FA and MNG when histopathological findings are equivocal.

High Mobility Group Box 1 (HMGB1) expression in gastric adenocarcinomas.

PURPOSE: High mobility group box 1 (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. The purpose of this study was to investigate the expression of HMGB-1 in gastric adenocarcinoma (GC) and to evaluate its diagnostic and prognostic value. METHODS: This study included 85 cases histopathologically diagnosed with GC. Sections obtained from formalin-fixed paraffin-embedded blocks were stained immunohistochemically with HMGB1 antibody. HMGB1 expression was compared with clinicopathologic and prognostic data. RESULTS: HMGB1 expression was negative in 16 (18.8%) patients and positive in 69 (81.2%) patients. There was no correlation between HMGB1 expression and age, sex, histologic subtype of tumor, lymph node involvement (p=0.455, p=0.365, p=0.448, p=0.077, respectively ). There was a significant correlation between HMGB1 expression and tumor grade, local invasion depth (T stage) and pTNM stage (p=0.016, p=0.022, p=0.015, respectively). CONCLUSION: It was found that in the presence of HMGB1 expression, the grade of tumor differentiation decreased and the depth of invasion increased, which was associated with higher stage. These findings suggest that HMGB1 is an independent prognostic factor for GC.

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.

The Frequency of Primary Sjogren's Syndrome and Fibromyalgia in Irritable Bowel Syndrome.

OBJECTIVE: To determine the frequency of sicca complex, Sjogren's Syndrome (SS) and Fibromyalgia (FM) in patients with Irritable Bowel Syndrome (IBS). METHODS: Seventy seven IBS patients who fulfilled the Rome-III criteria were included in the study. All patients were assessed for FM according to the American College of Rheumatology (ACR) 2010 criteria. After examination for objective evidence of sicca complex by Schirmer test, TBUT and Ocular Staining Score (OSS), serological tests were performed. And the diagnosis of SS was made according to the American College of Rheumatology (ACR) classification criteria for SS - 2012. RESULTS: Thirteen (16.9%) of IBS patients had FM. Dry eye was detected in 20(26.0%), 7(9.1%) and 29(37.7%) patients by OSS, Schirmer test and TBUT, respectively. Of 77 patients with IBS, the diagnosis of SS was established in two patients (2.6%). CONCLUSION: The frequency of Sjogren's Syndrome among patients with IBS is relatively higher than the general population. All IBS patients should be questioned for dryness of the mouth and eyes, and if necessary, should be evaluated for SS.

VEGF receptor subtypes may serve as novel prognostic factors and putative indicators for anti VEGF receptor treatment response in renal cell carcinoma cases.

PURPOSE: Targeted therapies are novel treatment options for renal cell carcinoma (RCC). Of the target molecules investigated, vascular endothelial growth factor receptors (VEFGRs) were seldom evaluated. The current study investigated the prognostic significance of VEGFRs and IMP-3 as a potential prognostic markers. METHODS: Pathological material and clinical files of 100 patients with RCC were retrospectively evaluated. For each case, the clinical outcome and disease stage were assessed and resected materials were histologically reevaluated. VEGFR-2, VEGFR-3 and IMP-3 expression of tumor samples were analyzed with immunohistochemistry. These expressions were compared with prognosis and clinicopathological variables. RESULTS: Five-year overall survival (OS) was 80% in the whole cohort. Mean survival was 20.3±1.9 months in metastatic disease (95%CI:16.4-24.2). Two-year OS was 20% and 5-year OS was zero in the metastatic group. Survival was significantly longer in VEGFR-2 expressing group than in the nonexpressing group (78.7±2.6 vs 63.9±6; 95%CI:73.7-84 and 52.1-75.7, respectively; p=0.031). VEGFR-3 and IMP-3 expressions were not significantly correlated with survival. In the non-metastatic group mean OS was 82.6±2.1 months and 2- and 5-year OS were 96 and 88%, respectively. CONCLUSIONS: Since VEGFRs were expressed on all histological subtypes and significantly correlated with survival, assessment of VEGFR-2 and VEGFR-3 on tumor samples might serve as a putative prognostic factor in RCC cases. These expressions might identify a subset of patients that may benefit from antiangiogenic treatments targeting VEGFR receptors.

Ultrasonography for the prediction of extension of trophoblastic infiltration into the tubal wall in ampullary pregnancy.

OBJECTIVE: Predictive factors of damage to the Fallopian tube may guide the treatment for patients with tubal pregnancy. The purpose of this study was to evaluate the predictive value of ultrasonographic findings in patients affected by ampullary pregnancy for the determination of the depth of trophoblastic infiltration into the tubal wall on histological examination. MATERIAL AND METHODS: 38 patients with ampullary pregnancy undergoing salpingectomy were enrolled into the study. The patients were divided into two subgroups depending on their transvaginal sonography (TVS) findings; either an ectopic gestational sac containing an embryo with cardiac activity or those with a tubal ring. The ampullary pregnancies were histologically classified according to the depth of infiltration of trophoblastic tissue into the tubal wall as follows: stage I: limited to mucosa; stage II: extension to the muscularis layer; stage III: complete infiltration of the tubal wall with or without rupture of the serosa. The association between findings on TVS and stage of trophoblastic invasion, serum beta-human chorionic gonodatropin (ß-hCG) levels was evaluated. RESULTS: Although there was no significant difference among two groups in terms of histological stage of trophoblastic infiltration (p = 0.257), patients in whom an embryo with cardiac activity had been identified were found to have higher percentage of stage II (47.8%) or stage III (8.7%) invasion. However, there was a significant difference in serum ß-hCG levels on the day of surgery among the two groups (p = 0.028). CONCLUSIONS: Ultrasonographic aspect of ampullary pregnancy is associated with depth of trophoblastic infiltration into the tubal wall and serum ß-hCG levels.

Expression patterns of claudins 1, 4, and 7 and their prognostic significance in nasopharyngeal carcinoma.

PURPOSE: Tight junction (TJ) proteins in the cells organize paracellular permeability, and they have a critical role in apical cell-to-cell adhesion and epithelial polarity. In our study, the expression patterns of claudins 1, 4, and 7 and their relationship with prognosis were determined in patients with nasopharyngeal carcinoma. METHODS: Claudins 1, 4, and 7 were stained immunohistochemically in 18 biopsy samples of nasopharyngeal carcinomas that included non-neoplastic surface epithelium and dysplastic epithelium in addition to the tumor tissue. The files of these patients were scanned and the stage of disease and treatment received were obtained along with demographic data such as age and gender. RESULTS: Overexpression of claudins 1, 4, and 7 in non-neoplastic surface epithelium was found in 14 (77.7%), 16 (88.8%), and 10 (55.5%) cases respectively; in dysplastic surface epithelium overexpression was found in 8 (44.4%), 13 (72.2%), and 4 (22.2%) cases, respectively; and in invasive tumor areas overexpression was found in 13 (72.2%), 9 (50%), and 10 (55.6%) cases respectively. Increased claudin 4 expression was related to advanced stage (p=0.014). There was a significant relationship determined between claudin 4 and 7 expression and decreased survival (p=0.018, p=0.024, respectively). CONCLUSION: The fact that a statistically significant relationship was found between claudin 4 expression and advanced stage, and similarly a statistically significant relationship was found between claudin 4 & 7 expression and decreased survival gives rise to thoughts that especially claudin 4 and 7 could have different tumorigenic effects on nasopharyngeal carcinoma besides their known adhesion characteristics.

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.

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.

The relation of radiation-induced pulmonary fibrosis with stress and the efficiency of antioxidant treatment: an experimental study.

BACKGROUND: Radiation-Induced Lung Injury has 2 components: radiation pneumonitis and radiation fibrosis. The pulmonary fibrosis has no known efficient treatment. The purpose of this study was to study the relationship between the oxidant/antioxidant status and pulmonary fibrosis in rats having radiation induced pulmonary fibrosis and to study the antioxidant effects of pentoxifylline, vitamin E, and vitamin C in the treatment of pulmonary fibrosis. MATERIAL AND METHODS: The study rats were divided into 5 groups: Thoracic RT + vitamin E+ Pentoxifylline for group 1, Thoracic RT + vitamin C + Pentoxifylline for group 2, Thoracic RT + vitamin C + vitamin E + Pentoxifylline for group 3, and Thoracic RT + Pentoxifylline for group 4, and group 5 was the control group. RESULTS: When groups are evaluated in pairs, significant differences between group 1 and 2, group 1 and 4, and group 1 and 5 were determined (p: 0.002, p: 0.002, p<0.001, respectively). No significant difference was determined between group 1 and 3 (p: 0.161). No significant difference was determined between group 2 and group 3, 4, and 5 (p: 0.105, p: 0.645, p: 0.234, respectively). There was no significant difference between group 4 and 5 (p: 0.645). CONCLUSIONS: The combination of vitamin E and pentoxifylline is efficient in preventing radiation-induced lung fibrosis. The additional benefit of vitamin C, which is added to this combination to increase the antioxidant activity, cannot be shown. It would be useful to investigate the combination of vitamin E, pentoxifylline, and other non-enzymatic antioxidants.

Expression of cyclooxygenase-2 and Bcl-2 in breast cancer and their relationship with triple-negative disease.

PURPOSE: Carcinogenesis is a multistep process with many factors being involved. The aim of this study was to investigate the role of cyclooxygenase-2 (COX-2) and Bcl-2 expression in patients with triple-negative breast cancer (TNBC) and, also whether any differences exist between TNBC and non-TNBC patients in relation with these two parameters. METHODS: This study included 50 patients with pathologically diagnosed TNBC and followed up at the Medical Oncology Clinic of Antalya Education and Research Hospital between 2008 and 2010. Thirty non-TNBC patients composed the control group. COX-2 and Bcl-2 expression was immunohistochemically investigated in both patient groups. RESULTS: COX-2 expression was positive in 26 (86.7%) of non-TNBC and 18 (90%) of TNBC patients (p=0.722). Compared with non-TNBC, TNBC correlated with higher Bcl-2 expression (p=0.005). Of the non-TBNC patients 86.7% and 50% of TNBC patients showed Bcl-2 expression. When Bcl-2 and COX-2 expression were considered together, a significant difference was found between the two groups (p=0.021). CONCLUSION: This study showed that increased COX-2 expression correlated with Bcl-2 expression both in TNBC and non-TNBC patients. Analysis of coexpression of Bcl- 2 and COX-2 may be meaningful for deciding treatment strategies for TNBC. Treatment strategies targeting Bcl-2 and COX-2 seem to be promising for this aggressive disease with no specific treatment.

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.

Stem cell-related markers in primary breast cancers and associated metastatic lesions.

It has been reported previously that: (1) normal-breast epithelial cells that are CD24-/44+ express higher levels of stem/progenitor cell-associated genes; (2) cancer cells that have undergone epithelial to mesenchymal transition display CD24-/44+ cell-surface expression, a marker for breast cancer stem cells; (3) loss of E-cadherin is a preliminary step in epithelial to mesenchymal transition; and (4) vimentin is a marker of mesenchymal phenotype. We hypothesized that stem cell subpopulations would be more frequent in metastatic than in primary tumors. Therefore we assessed by immunohistochemical analysis, tissue microarrays containing tissue from primary and associated metastatic breast cancers for expression of CD24, CD44, E-cadherin and vimentin to evaluate candidate cancer-initiating cell populations in breast cancer subtypes and metastatic lesions. The occurrence of CD24-/44+ and CD24+/44- cells did not differ in primary vs matched lymph node or distant and locoregional metastatic lesions; E-cadherin expression was decreased in primary vs lymph node metastases (P=0.018) but not decreased in distant and locoregional metastases relative to primary tumor, whereas vimentin, was more frequently expressed in lymph node and distant and locoregional metastases (P=0.013, P=0.004) than in matched primary cancers. Thus, the frequency of CD24-/44+ cells does not differ in metastases relative to the primary breast cancer but differs by tumor stage and subtype.

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.

Aberrant expression of DNA damage response proteins is associated with breast cancer subtype and clinical features.

Landmark studies of the status of DNA damage checkpoints and associated repair functions in preneoplastic and neoplastic cells has focused attention on importance of these pathways in cancer development, and inhibitors of repair pathways are in clinical trials for treatment of triple negative breast cancer. Cancer heterogeneity suggests that specific cancer subtypes will have distinct mechanisms of DNA damage survival, dependent on biological context. In this study, status of DNA damage response (DDR)-associated proteins was examined in breast cancer subtypes in association with clinical features; 479 breast cancers were examined for expression of DDR proteins γH2AX, BRCA1, pChk2, and p53, DNA damage-sensitive tumor suppressors Fhit and Wwox, and Wwox-interacting proteins Ap2α, Ap2γ, ErbB4, and correlations among proteins, tumor subtypes, and clinical features were assessed. In a multivariable model, triple negative cancers showed significantly reduced Fhit and Wwox, increased p53 and Ap2γ protein expression, and were significantly more likely than other subtype tumors to exhibit aberrant expression of two or more DDR-associated proteins. Disease-free survival was associated with subtype, Fhit and membrane ErbB4 expression level and aberrant expression of multiple DDR-associated proteins. These results suggest that definition of specific DNA repair and checkpoint defects in subgroups of triple negative cancer might identify new treatment targets. Expression of Wwox and its interactor, ErbB4, was highly significantly reduced in metastatic tissues vs. matched primary tissues, suggesting that Wwox signal pathway loss contributes to lymph node metastasis, perhaps by allowing survival of tumor cells that have detached from basement membranes, as proposed for the role of Wwox in ovarian cancer spread.