The prognostic significance of the heterologous component in uterine carcinosarcomas.

OBJECTIVE: Uterine carcinosarcomas are aggressive, rare biphasic tumors with malignant epithelial and malignant sarcomatous components. The prognostic significance of the presence of extrauterine sarcoma (heterologous component) is controversial. Therefore, the aim of this study was to investigate the effect of heterologous components in uterine carcinosarcomas on disease-free survival, overall survival, and other prognostic factors. METHODS: Clinical and histopathological data from patients treated for uterine carcinosarcoma in a tertiary cancer center in Turkey between July 2000 and January 2020 were collected. Independent risk factors affecting overall survival and disease-free survival were analyzed by univariate and multivariate Cox regression analyses. RESULTS: A total of 98 patients were identified. The median follow-up was 21.8 (1.2-233.1) months. In the multivariate analysis, the median overall survival and disease-free survival were 23.8 and 20.7 months in those with homologous mesenchymal components and 17.6 and 9.7 months in those with heterologous mesenchymal components, respectively. It was found that the presence of heterologous mesenchymal components significantly reduced both overall survival and disease-free survival (odds ratio [OR], 2.861; 95% confidence interval [CI] 1.196-6.841; p=0.018 and OR, 3.697; 95%CI 1.572-8.695; p=0.003, respectively). In addition, both lymphadenectomy and adjuvant radiotherapy were found to significantly increase overall survival and disease-free survival. Age was found to increase only disease-free survival. CONCLUSION: The results obtained in this study showed that the presence of heterologous components in uterine carcinosarcoma is a prognostic factor that adversely affects both overall survival and disease-free survival. Lymphadenectomy and adjuvant radiotherapy have beneficial effects on both overall survival and disease-free survival.

The prognostic significance of the heterologous component in uterine carcinosarcomas

SUMMARY OBJECTIVE: Uterine carcinosarcomas are aggressive, rare biphasic tumors with malignant epithelial and malignant sarcomatous components. The prognostic significance of the presence of extrauterine sarcoma (heterologous component) is controversial. Therefore, the aim of this study was to investigate the effect of heterologous components in uterine carcinosarcomas on disease-free survival, overall survival, and other prognostic factors. METHODS: Clinical and histopathological data from patients treated for uterine carcinosarcoma in a tertiary cancer center in Turkey between July 2000 and January 2020 were collected. Independent risk factors affecting overall survival and disease-free survival were analyzed by univariate and multivariate Cox regression analyses. RESULTS: A total of 98 patients were identified. The median follow-up was 21.8 (1.2-233.1) months. In the multivariate analysis, the median overall survival and disease-free survival were 23.8 and 20.7 months in those with homologous mesenchymal components and 17.6 and 9.7 months in those with heterologous mesenchymal components, respectively. It was found that the presence of heterologous mesenchymal components significantly reduced both overall survival and disease-free survival (odds ratio [OR], 2.861; 95% confidence interval [CI] 1.196-6.841; p=0.018 and OR, 3.697; 95%CI 1.572-8.695; p=0.003, respectively). In addition, both lymphadenectomy and adjuvant radiotherapy were found to significantly increase overall survival and disease-free survival. Age was found to increase only disease-free survival. CONCLUSION: The results obtained in this study showed that the presence of heterologous components in uterine carcinosarcoma is a prognostic factor that adversely affects both overall survival and disease-free survival. Lymphadenectomy and adjuvant radiotherapy have beneficial effects on both overall survival and disease-free survival.

Tissue Expression of Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 in Breast Cancers.

Objective: Breast cancer is the most common cancer among women worldwide. Neutrophil gelatinase-associated lipocalin (NGAL) has important roles in immunity, cell proliferation, and carcinogenesis. Kidney injury molecule-1 (KIM-1) is a transmembrane glycoprotein also known as hepatitis A virus cellular receptor 1 and T-cell immunoglobulin and mucin, has restricted expression in immune cells and healthy epithelial cells, but it is up-regulated in several human cancers. The aim of this study was to determine the prognostic values of NGAL and KIM-1 expression in tumor cells and to detect the presence of NGAL-positive neutrophils (PNL) in the tumor microenvironment. Materials and Methods: The expression of NGAL and KIM-1 protein were assessed by immunohistochemical staining in tissue specimens from 412 primary breast cancer cases. Results: In this series, the mean age of the patients was 55.6±12.4 years. In 218 (52.9%) cases, there was NGAL expression in tumor cells. In 104 (25.2%) cases there was KIM-1 expression in tumor cells. NGAL-positive inflammatory cells were seen in tumors of 45 (10.9%) cases. There was no significant relationship between NGAL-positive PNL presence in the tumor microenvironment and other clinicopathological features. However, there was a significant association between the presence of in situ carcinomas and NGAL expression (p = 0.008) and KIM-1 expression (p = 0.020) in tumor cells. Conclusion: This study has demonstrated positivity of NGAL and KIM-1 in breast cancer cells. Considering the development of anti-KIM-1 therapies, the presence of KIM-1 expression may be a new treatment option in breast cancer, especially in in situ component-rich tumors. These findings should be confirmed in larger series.

Evaluation of the Prognostic Significance of Cereblon Protein Expression in Multiple Myeloma.

BACKGROUND: Considerable progress has been made in the treatment of multiple myeloma (MM) patients with the development of various new agents that increased survival rates over the past fifteen years. Cereblon (CRBN) plays an important role in mediating the antitumor effects of immunomodulatory drugs (IMiDs) among these new agents. The aim of our study is to investigate immunohistochemically (IHC) cereblon protein expression status in MM. METHODS: Immunohistochemically, CRBN expression and its relationship with various prognostic factors were evaluated in bone marrow biopsies of 96 patients with MM in a single centre. RESULTS: Cytoplasmic and nuclear CRBN expression was detected in all neoplastic cells. While a complete or partial response to treatment was obtained in 45 patients, the disease was stable in 13 and progressive in 17 patients. Survival was longer in those treated with IMiD-containing regimens (p = 0.044). Both the survival rate (p = 0.013) and the survival time were significantly increased (p = 0.023) in those who received the treatment protocol containing protease inhibitors. A significant relationship was found between the treatment protocol and treatment response in the chi-squared analysis (p = 0.008). Although the longest survival time - though not statistically significant - was detected in the group treated with protease inhibitors (log rank, p = 0.217). The survival analysis revealed the presence of a relationship between IgG and IgA positivity and survival. CONCLUSIONS: In this study, the survival time of the patients who received treatment regimens containing protease inhibitors and IMiD was longer, independent of the presence of strong nuclear CRBN expression. The survival rate was significantly higher in those who used IMiD and protease inhibitors in combination. Since the survival rate was found to be increased in IgG positive cases and we thought that evaluation of immunoglobulin tissue expression in MM cases can provide prognostic prediction.

Analysis of vanishing endometrial cancer by pathological types.

PURPOSE: We asked why endometrial cancer sometimes vanishes. METHODS: A total of 454 patients diagnosed with endometrioid-type endometrial cancer (EC) (via endometrial sampling) and treated in our clinic over the past 5 years were enrolled. The patients were divided into two groups: vanishing and residual, depending on whether a tumor was detected in the postoperative hysterectomy specimen. Patient age, numbers of pregnancies and deliveries, menopausal status, systemic disease status, hemogram parameters, International Federation of Gynecology and Obstetrics (FIGO) grade, and invasion status (evident on magnetic resonance imaging [MRI]) were compared between the groups. RESULTS: ECs vanished in 42 (9.25%) patients. The vanishing rates were 19.7% (37/187) in FIGO grade 1 patients, 2.1% (5/238) in grade 2 patients, and 0% (0/29) in grade 3 patients. The average age was lower in the vanishing than the residual group, but the premenopausal status and grade 1 tumor rates were higher (both p < 0.001). An absence of invasion (as revealed by MRI) was more common in the vanishing group (p < 0.001). No recurrence developed in the vanishing group, but recurrences were noted in 3.3% (14/412) of the residual group. There were no significant between-group differences in any of the numbers of pregnancies or births, systemic disease status, or hemogram parameters (all p > 0.05). CONCLUSION: Vanishing EC is more likely in premenopausal women with endometrioid grade 1 EC (as revealed by endometrial biopsy) who lack myometrial invasion on MRI.

Neuroendocrine carcinoma of the endometrium: A very rare gynecologic malignancy.

OBJECTIVE: To investigate the clinicopathologic characteristics, prognostic factors, outcome, and treatment of the neuroendocrine carcinoma (NEC) of the endometrium. MATERIALS AND METHODS: We retrospectively reviewed the clinicopathologic and survival data of 10 patients who underwent surgery for NEC. The patients were collected between 1999 and 2017 from four referral centers in Turkey. RESULTS: The median age of patients was 67 years (range: 34-75 years). The NEC of endometrium consist of 9 cases with small cell carcinoma (SC) NEC (two with mixed histotypes), and one with a large cell (LC) NEC. According to FIGO 2009 criteria, 70 % (7/10) of patients had advanced stage (III and IV) disease. All patients except one underwent surgical staging, eight patients received platinum-based chemotherapy (CTX) and of 6 those were additionally treated with radiotherapy (RT). Four patients died of disease ranging from 2 to 10 months and six were alive 12-72 months with no evidence of disease. In addition, 4 SC NEC cases raised in polypoid features had no evidence of disease from 24 to 72 months. DISCUSSION: NEC of the endometrium is a rare disease with poor prognosis, which frequently diagnosed in advanced stages. The main treatment modality was the administration of platinum-based CTX as an adjuvant to surgery or surgery and RT. Our result suggests that the polypoid feature of the tumor might be one of the best predictors for the prognosis of SC NEC.

Loss of Nuclear ARID-1A Expressions Is Associated with Hormone Receptor Status in Breast Cancers.

OBJECTIVE: Breast cancer is the most common cancer among women worldwide. Adenine thymine-rich interactive domain 1A (ARIDIA) is a tumor suppressor gene involved in chromatin remodeling and it encodes the ARIDIA protein. Recent studies have shown the loss of ARIDIA protein expression in different carcinomas may have a prognostic significance. In the present study, we aimed to evaluate the interactions between ARIDIA loss and molecular subtypes of breast carcinomas. MATERIALS AND METHODS: ARIDIA expressions were studied in 292 formalin- fixed, paraffin- embedded breast carcinoma specimens and its association with different pathological and clinical parameters was evaluated. RESULTS: Loss of ARIDIA expression was detected in 123 cases. There was no statistically significant association between ARID-1A expression and molecular subtype of breast carcinomas (p=0.110) or HER2 amplification (p=0.909). Contrarily, there was a significant association between ARIDIA expression and presence of estrogen (p=0.047) or progesterone receptors (p=0.023). Besides a statistically significant relationship was found between loss of ARID1A, and the presence of both in situ component (p=0.016) and lymph node metastasis (p=0.001). CONCLUSION: In this study, we have demonstrated that loss of ARID1A expression positively correlates with hormone receptor status as well as tumor aggressiveness.

Klippel-Trenaunay-Weber Syndrome with Atypical Presentation of Cerebral Cavernous Angioma: A Case Report and Literature Review.

BACKGROUND: Klippel-Trenaunay-Weber syndrome (KTWS) is a rare syndrome characterized by the triad of cutaneous hemangiomas, venous varicosities, and osseous-soft tissue hypertrophy of the affected limb. Clinical manifestations, genetic testing, and radiologic imaging are the key steps in diagnosing this syndrome. CASE DESCRIPTION: An 18-month-old boy was brought for follow-up brain magnetic resonance imaging (MRI) with a history of right lower limb hypertrophy, cutaneous varicosities, and hemangiomas diagnosed at birth. A baseline MRI at 12 months revealed multiple hemorrhagic lesions within the cerebrum, the largest in the right temporal lobe, which was treated surgically at the age of 18 months because of its rapid growth. This is the youngest patient with KTWS treated surgically for intracranial hemangiomas. CONCLUSION: KTWS is a rare disease with a wide range of manifestations. Multisystemic evaluation of this group of patients should be performed to identify cavernous hemangiomas at the early stage of life and adequately treat them in the future. Treatment of KTWS patients with cavernous hemangiomas should not be different from the treatment of patients with any other hemangiomas, and surgical intervention should be considered on a case-to-case bases.

The prognostic significance of pdl1 and foxp3 expressions in tumor cells and the tumor microenvironment of ovarian epithelial tumors.

BACKGROUND: The aim of this study is to determine the prognostic values of PDL1 expression in ovarian epithelial tumors and to detect the presence of FOXP3-positive T reg cells in the tumor microenvironment. METHODS: This study included patients with benign, borderline or malignant ovarian serous tumors (n=82), mucinous cancer (n=17) and endometrioid cancer (n=36). FOXP3 and PDL1 were immunohistochemically evaluated and compared with histopathological and clinical prognostic parameters. RESULTS: There was no expression of PDL1 in any tumor cell. However, PDL1-positive inflammatory cells were seen in 10 cases (7.3%) with mucinous carcinoma (n=6), endometrioid carcinoma (n=2), borderline (n=1), and benign (n=1) serous tumors. It was also determined that there was a significant positive correlation between PD-L1 expression in tumor infiltrating cells and survival (P<0.01). In 47 (34.3%) cases, there were FOXP3-positive cells. The number of FOXP3-positive cells was significantly higher in ovarian cancer, especially in serous and endometrioid carcinomas, rather than benign and borderline tumors (P=0.007). But there was no statistically significant association between the survival times and the presence of T regs (P=0.241). CONCLUSIONS: This study demonstrated that the presence of FOXP3 and PDL1-positive regulatory T cells in TILs was associated with mainly malignant tumors. We also found that the presence of PD-L1-positive inflammatory cells has a positive effect on survival.

Tissue expression of human epididymal secretory protein 4 may be useful in the differential diagnosis of uterine cervical tumors.

OBJECTIVES: Human Epididymal Secretory Protein 4 was firstly described as an epididymis-specific protein but more recently it has been demonstrated to be a putative serum tumor marker for different malignancies, especially ovarian epithelial cancers. The aim of this study is to investigate the association between tissue Human Epididymal Secretory Protein 4 expression and the clinicopathological features of uterine cervical tumors. MATERIAL AND METHODS: This retrospective study was designed to evaluate the differences of tissue expressions of Human Epididymal Secretory Protein 4 protein in a spectrum of cervical neoplasms. One hundred and seven patients recently diagnosed as having cervical intraepithelial neoplasm or invasive squamous cell carcinoma, adenosquamous carcinoma and adenocarcinoma based on pathology databases. RESULTS: Decreased or negative Human Epididymal Secretory Protein 4 expressions were determined in both normal cervical epithelia and in intraepithelial carcinomas, while increased HE4 expression was observed in invasive tumors. CONCLUSIONS: This study demonstrated that altered expression of Human Epididymal Secretory Protein 4 may involve in tumorigenesis in the uterine cervix. Our findings also suggested the presence of a correlation between Human Epididymal Secretory Protein 4 expression and the invasive potential of uterine tumors. Therefore it may be thought that the tissue expression of HE4 can be used to differentiate high grade intraepithelial tumors from carcinomas.

The evaluation of the caveolin-1 and AT-rich interactive domain 1 alpha expressions in uterine smooth muscle tumors.

OBJECTIVES: This retrospective study was designed to evaluate the importance of tissue expressions of caveolin-1 (Cav-1) and AT-rich interactive domain 1 alpha (ARID-1A) which are known as signal regulator and tumor suppressor in differential diagnosis of uterine smooth muscle tumors (SMTs). MATERIALS AND METHODS: Thirty patients recently diagnosed as uterine SMTs at the Tepecik Training and Research Hospital were identified using pathology databases. Immunohistochemical stains for Cav-1 and ARID-1A were performed. RESULTS: In this series, there were 10 leiomyosarcomas (LMSs), 10 uterine smooth muscle tumors of uncertain malignant potentials (STUMPs), and 10 leiomyomas (LMs). Cav-1 expression located cytoplasmic or perivascular area. Cytoplasmic Cav-1 expression was determined in 5 LMSs and 2 STUMPs while perivascular Cav-1 expression was determined in 9 LMSs and 2 STUMPs. Statistically, it was determined that if the tumor becomes malignant and more invasive, it gains the perivascular Cav-1 expression (P = 0.029). On the other hand, the mean nuclear staining rate for ARID-1A in LMSs (63 ± 23.4%) was higher than both STUMPs (60 ± 18.5%) and LMs (34.5 ± 16.5%). Statistically, it was determined that the expression of ARID-1A was significantly downregulated in LMs when compared with STUMPs and LMSs (P = 0.004). CONCLUSIONS: Our findings were demonstrated that perivascular Cav-1 expression was seen to be a marker for malignancy of uterine SMTs. Similarly, we found to link of ARID-1A expression and the aggressiveness of SMTs. Therefore, it may be suggested that Cav-1 and ARID-1A may act as predictive biomarkers in uterine SMTs.

Synchronous primary endometrial and ovarian cancers: a multicenter review of 63 cases.

AIMS: To investigate clinicopathologic characteristics, therapeutic methods, and prognostic factors in women with synchronous primary endometrial and ovarian cancers (SEOCs). METHODS: A retrospective review of 2 cancer registry databases in Turkey was conducted to identify patients diagnosed with SEOCs between January 1995 and December 2012. Patients with recurrent, metastatic, and metachronously occurring tumors were excluded. Multivariate logistic regression models were used to identify prognostic predictors for progression-free survival (PFS) and overall survival (OS). RESULTS: The analysis included 63 women with SEOCs. Seventy-six percent of the patients had stage I endometrial cancer, and 60% of the patients had stage I ovarian cancer. Thirty-seven patients (58.7%) had endometrioid/endometrioid histology. Optimal cytoreduction was obtained in 47 (74.6%) patients. Recurrence developed in 17 patients (27%). Multivariate analysis confirmed lymphovascular space invasion (LVSI) as an independent poor prognostic factor for OS (odds ratio [OR] 3.1, p = 0.045), whereas early-stage disease and optimal cytoreduction were found to be independent good prognostic factors for both PFS (OR 12.85, p<0.001 and OR 4.58, p = 0.004, respectively) and OS (OR 7.31, p = 0.002 and OR 2.95, p = 0.028, respectively). The 3- and 5-year OS rates were 74% and 69%, respectively. CONCLUSIONS: Our study demonstrated that optimal cytoreduction, early-stage disease, and LVSI are the most significant factors affecting survival in women with SEOC.

Differences in the ARID-1 alpha expressions in squamous and adenosquamous carcinomas of uterine cervix.

AT-rich interactive domain 1A (ARID1A) is a tumor suppressor gene involved in chromatin remodeling which encodes ARID1A (BAF250a) protein. Recent studies have shown the loss of ARID1A expression in several types of tumors. This retrospective study was designed to evaluate the differences in tissue expressions of ARID1A in a spectrum of cervical neoplasms. Cervical intraepithelial neoplasms, invasive squamous or adenosquamous carcinomas were identified in 100 patients recently diagnosed as cervical neoplasms based on pathology databases. In this series, there were 29 low- and 29 high-grade cervical intraepithelial neoplasms, 27 squamous cell carcinomas, and 15 adenosquamous carcinomas. Mean age of the patients was 47.8 ± 13 years (20-80 years). It was determined that the expression of ARID1A was statistically significantly down-regulated in adenosquamous carcinomas when compared with non-invasive or invasive squamous cell carcinomas (p = 0.015). Lower levels of the ARID1A expression were detected in cases with adenosquamous carcinomas (60%), low- or high-grade squamous intraepithelial lesion (SIL) (31%), and squamous cell carcinomas (18.5%). Our findings have demonstrated the presence of a correlation between ARID1A expression and adenomatous differentiation of uterine squamous cell carcinomas. Therefore, ARID1A gene may suggestively have a role in the pathogenesis of cervical adenosquamous carcinomas.

Expression of caveolin-1 in peritumoral stroma is associated with histological grade in ovarian serous tumors.

BACKGROUND: Previous studies have demonstrated that Caveolin-1 (Cav-1) can ambiguously behave as tumor suppressor or tumor promoter in different neoplasms, depending on cancer type. Some findings have also revealed that cell proliferation, migration and invasion were attenuated by the knockdown of Caveolin-1 expressions. However, the functional and prognostic significance of Caveolin-1 in most tumors remains to be fully elucidated. OBJECTIVES: The aim of the study was to investigate a possible association between tissue Caveolin-1 expression and the clinicopathologic features of ovarian serous tumors. MATERIAL AND METHODS: Caveolin-1 expression was studied in a total of 82 formalin-fixed, paraffin-embedded specimens of ovarian serous tumors and its association with different clinicopathologic parameters was evaluated. RESULTS: The study included 36 (43.9%) benign, 12 (14.6%) borderline and 34 (41.5%) malignant serous tumors. Mean patient age was 43.9 ± 14.4 years (17-72 years). Statistical analysis revealed that if the tumor becomes more aggressive and invasive, it losses the stromal Caveolin-1 expression (p = 0.001). Also, parallel changes between stromal and perivascular Caveolin-1 expressions were observed. CONCLUSIONS: Our findings demonstrated a link between Caveolin-1 expression and the aggressiveness of ovarian cancer. Therefore, it seems safe to suggest that Cav-1 may act as a differential diagnostic biomarker in ovarian serous tumors.

An analysis of 37 patients with uterine leiomyosarcoma at a high-volume cancer center.

OBJECTIVE: To evaluate the clinicopathologic characteristics, treatment methods, survival, and prognosis of uterine leiomyosarcoma (ULMS). MATERIALS AND METHODS: All patients with ULMS who were treated between January 1998 and October 2012 were retrospectively reviewed. A total of 37 women who met the inclusion criteria were included in the present study. Univariate and multivariate analyses were used to identify the risk factors for overall survival (OS) and progression-free survival (PFS). RESULTS: The majority of patients had stage 1 disease (IA, n=9 (24.3%); IB, n=23 (62.1%)). All patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Additionally, only pelvic, and pelvic plus para-aortic lymphadenectomy was performed in 5 (13.5%) and 8 (21.6%) women, respectively. Adjuvant treatment was administered to 27 (72.9%) patients. Patients who did not receive adjuvant therapy had stage 1 disease. Recurrences occurred in 5 (13.5%) patients. The median follow-up period was 71 months (range 1-158 months). The 5-year PFS and OS rates were 68% and 74%, for all patients. The 5-year OS rates for women with stage 1 and ≥ stage 2 disease were 82% and 27%, respectively. Multivariate analysis confirmed stage 1 disease as the only independent predictor of both PFS (Odds ratio (OR) 10.955, 95% confidence interval (CI) 1.686-71.181, (p=0.012)) and OS (OR 57.429, 95% CI 3.287-1003.269, (p=0.006)). CONCLUSIONS: Extensive surgery is not associated with prognosis and stage 1 disease is the only independent good prognostic factor for survival in patients with ULMS.

Adjuvant treatment modalities, prognostic predictors and outcomes of uterine carcinosarcomas.

PURPOSE: The purpose of this study is to evaluate the clinicopathological characteristics, treatment, and prognosis of uterine carcinosarcoma (UC). MATERIALS AND METHODS: A retrospective review of three cancer registry databases in Turkey was conducted for identification of patients diagnosed with UC between January 1, 1996, and December 31, 2012. We collected clinicopathological data in order to evaluate factors important in disease- free survival (DFS) and overall survival (OS). RESULTS: A total of 66 patients with UC with a median age of 65.0 years were included in the analysis. The median survival time of all patients was 37.5 months and the 5-year OS rate was 59.1%. In early stage patients (I-II) who received adjuvant chemotherapy (CT) with radiation therapy (RT), the median DFS and OS was 44 months and 55 months, respectively, compared to 34.5 months and 36 months, respectively, in patients who received adjuvant RT or CT alone (hazard ratio [HR], 1.4; 95% confidence interval [CI], 0.7 to 3.1 for DFS; p=0.23 and HR, 2.2; 95% CI, 0.9 to 5.3 for OS; p=0.03). In advanced stage patients (III-IV), the median DFS and OS of patients receiving adjuvant RT with CT was 25 months and 38 months, respectively, compared to 23.5 months and 24.5 months, respectively, in patients receiving adjuvant RT or CT alone (HR, 3.1; 95% CI, 0.6 to 16.0 for DFS; p=0.03); (HR, 3.3; 95% CI, 0.7 to 15.0 for OS; p=0.01). In multivariate analysis, advanced International Federation of Gynecology and Obstetrics (FIGO) stage and suboptimal surgery showed significant association with poor OS. CONCLUSION: In patients with early or advanced stage UC, adjuvant CT with RT is associated with improved DFS and OS, as compared to CT or RT alone.

Significance of apoptosis related proteins on malignant transformation of ovarian tumors: A comparison between Bcl-2/Bax ratio and p53 immunoreactivity.

In this study, we compared the immunoreactivities of Bcl-2, Bax and p53 proteins in ovarian tumors and related the immunohistochemical findings to the histological type of the tumors. Formalin-fixed, paraffin wax-embedded tissue sections from 40 patients who had serous-mucinous borderline tumors and serous-mucinous adenocarcinoma of the ovary (n=10 each) were stained with hematoxylin-eosin (H&E). After histopathological examination, serial sections were stained immunohistochemically with primary antibodies to Bcl-2, Bax and p53 using an avidin-biotin-peroxidase method. A semi-quantitative grading system was used to compare the immunohistochemical staining intensities. The nuclear DNA fragmentation of apoptosis was determined using TUNEL method. As a result of immunohistochemical staining, increased immunoreactivity of Bcl-2 was observed in adenocarcinomas when compared to borderline tumors (P<0.001). Strong immunoreactivity of Bcl-2 and mild immunoreactivities of Bax and p53 were detected in ovarian adenocarcinomas. There were no significant statistical differences in the immunoreactivity of Bax among the histological type of ovarian tumors. Whereas a balance was observed between the immunoreactivities of Bcl-2 and Bax in the borderline cases, and this balance was strongly changed toward the anti-apoptotic Bcl-2 protein in patients with adenocarcinoma. TUNEL staining of sections indicated apoptotic cells in the serous borderline tumors were about 8-fold higher than in the serous adenocarcinoma. The results of this study on apoptosis-related factors might help to develop novel protective and therapeutic approaches, such as isoflavonoids and isothiocyanates, which were associated with decreased Bcl-2/Bax ratio, against the malignant epithelial ovarian tumors.

Immunolocalization of ERK1/2 and p-AKT in normal endometrium, endometrial hyperplasia, and early and advanced stage endometrioid endometrial adenocancer and their prognostic significance in malignant group.

OBJECTIVE: To analyze the expression patterns of extracellular signal-regulated kinase (ERK1/2) and phosphorylated (p)-AKT in the tissues of non-pathologic endometrium, endometrial hyperplasia, and early and advanced stage endometrioid endometrial adenocancer using indirect immunohistochemistry, and also to investigate the effect of ERK1/2 and p-AKT expression patterns on prognosis in endometrioid adenocancer. STUDY DESIGN: Immunolocalization of ERK1/2 and p-AKT was examined in six different types of endometrial tissues: proliferative endometrium (PE; n=10, 11.2%), secretuar endometrium (SE; n=10, 11.2%), simple hyperplasia (SH; n=15, 16.9%), complex hyperplasia (CH; n=3, 3.4%) and atypical complex hyperplasia (ACH; n=10, 11.2%), which were obtained from endometrial biopsies, curettage materials, and hysterectomy specimens and classified as the benign group; and both early stage endometrioid (n=21, 23.6%) and advanced stage endometrioid adenocancer (AC; n=20, 22.5%), which were obtained from complete surgical staging materials and classified as the malignant group. All specimens were fixed in 10% formalin and processed using routine paraffin protocols. Immunostaining intensities were evaluated as negative or weak (assigned as low expression) and moderate or strong (assigned as high expression). RESULTS: In the malignant group, 23 of 41 patients (56.1%) had high ERK1/2 and p-AKT expression, whereas only three of 48 patients in the benign group (6.3%) had high ERK1/2 and p-AKT expression (P<0.0001 and P<0.0001, respectively). p-AKT expression was significantly higher in women with positive lymph nodes (OR 9.0; 95% CI: 1.2-100.0; P=0.03). Higher expression of p-AKT was significantly associated with poor progression-free survival (PFS) and overall survival (OS). In contrast, ERK1/2 expression was not associated with PFS or OS.Conclusions ERK1/2 and p-AKT can be useful in the differential diagnosis of benign vs. malignant endometrial lesions, as well as early vs. advanced stage endometrioid endometrial adenocancer. Additionally, higher p-AKT expression could be used as a marker of poor prognosis in the management of patients with endometrioid endometrial adenocancer.

A pitfall in transrectal prostate biopsy: malakoplakia evaluation of two cases based on the literature review.

Malakoplakia is a rarely seen inflammatory condition that is considered to develop secondary to a chronic Escherichia coli infection. Although malakoplakia usually affects the genitourinary tract, it may also be observed in the colon, stomach, lungs, liver, bones, uterus, and skin. Malakoplakia of the genitourinary system usually involves the bladder, whereas it may also affect the prostate along with the bladder. Malakoplakia of the prostate is very rare, and it may be clinically mistaken for prostatic malignancies. Definitive diagnosis is only possible through histopathological examination. This study elaborates on two patients who presented to our hospital in 2013 with high PSA levels. The primary clinical consideration was prostate carcinoma. However, these two cases were diagnosed as malakoplakia based on the results of histopathological analysis of the transrectal prostate biopsy specimen.

TGF-ßs and Smads activities at the site of failed neural tube in the human embryos.

AIM: Transforming growth factor ß (TGF-ß) and Smads control intracellular signaling pathways in neurulation. Although previously reported similar experimental animal studies, the aim of this human study is to investigate the expression of TGF-ß (1,2,3) and Smads (1,2,3,6,7) in aborted human fetuses with myeloschisis. MATERIAL AND METHODS: Twelve human fetuses with neural tube defect were obtained. They were stained with antibodies against TGF-ß1, TGF-ß2, TGF-ß3, Smad (1,2,3), Smad 6 and Smad 7 using the indirect immunohistochemical technique. RESULTS: We noted mild immune reactivity of TGF-ß1 and TGF-ß2 in the open neural plate, motor neurons and surrounding tissue. Strong immune reactivity of TGF-ß3 was shown in only open neural plate and surrounding tissue. Immunoreactivity of all Smads noted negative except Smad7. CONCLUSION: These results suggested at the site where the neural tube failed to close, TGF-ß 1,2 and Smads 1,2,3,6 do not continue their activity and decrease with internal timing of embryonic development. Additionally ectodermal layers are considered by embryo as "not closed wound" and TGF-ß3 activity may be an effort to repair the failed closure.