lncRNA XIST Interacts with Regulatory T Cells within the Tumor Microenvironment in Chronic Hepatitis B-Associated Hepatocellular Carcinoma.

OBJECTIVE: Alterations in the expression of several long non-coding RNAs (lncRNAs) have been shown in chronic hepatitis B-associated hepatocellular carcinoma (CHB-HCC). Here, we aimed to investigate the association between the expression of inflammation-associated lncRNA X-inactive specific transcript (XIST) and the type of inflammatory cells within the tumor microenvironment. MATERIAL AND METHODS: Twenty-one consecutive cirrhotic patients with CHB-HCC were included. XIST expression levels were investigated on formalin-fixed paraffin-embedded (FFPE) tumoral and peritumoral tissue samples by real-time polymerase chain reaction (RT-PCR). Immunohistochemical staining for CD3, CD4, CD8, CD25, CD163, CTLA4, and PD-1 were performed. The findings were statistically analyzed. RESULTS: Of the 21 cases, 11 (52.4%) had tumoral and 10 (47.6%) had peritumoral XIST expression. No significant association was found between the degree of inflammation and XIST expression. The number of intratumoral CD3, CD4, CD8 and CD20 positive cells was higher in XIST-expressing tumors, albeit without statistical significance. Tumoral and peritumoral XIST expression tended to be more common in patients with tumoral and peritumoral CD4high inflammation. The number of intratumoral CD25 positive cells was significantly higher in XIST-expressing tumors (p=0.01). Tumoral XIST expression was significantly more common in intratumoral CD25high cases (p=0.04). Peritumoral XIST expression was also more common among patients with CD25high peritumoral inflammation, albeit without statistical significance (p=0.19). CONCLUSION: lncRNA XIST is expressed in CHB-HCC and its expression is significantly associated with the inflammatory tumor microenvironment, particularly with the presence and number of CD25 (+) regulatory T cells. In vitro studies are needed to explore the detailed mechanism.

The Prognostic Significance of Circulating Tumor Cells in Patients with Pancreatobiliary Cancer.

BACKGROUND: Circulating tumor cells (CTCs) are cancer cells which separate from the primary tumor and enter systemic circulation. In this study, it was aimed to examine the relationship between CTCs isolated and identified from the peripheral blood of patients with pancreatobiliary cancer, with the clinicopathological characteristics of the patients and their overall survival. METHODS: A total of 21 patients were included the study. Density gradient centrifugation with the OncoQuick® assay was performed for isolation of CTCs from peripheral blood. In order to identify CTCs, enriched samples underwent flow cytometric analysis. RESULTS: The rate of patients with positive surgical margin in the high CTC group (CTC <15) was identified to be statistically significantly high compared to the group with low CTC (CTC ≤15) (83.3% vs. 16.7%; P = .041). Median neutrophil/lymphocyte ratio (NLR) was found to be higher in the high CTC group compared to the low CTC group, which was close to statistical significance (2.37 vs. 1.41; P = .055). CONCLUSIONS: Circulating tumor cells were identified to have a significant relationship with surgical margin positivity in our study for the first time, suggesting that the CTCs count in peripheral blood in preoperative patients may be a biomarker predicting positive surgical margin. Due to the very low number of studies assessing the relationship between CTCs and NLR, our study which identified relationship close to statistical significance between CTCs and NLR, significantly contributes to the literature on the topic of the possible role of lymphocytes in CTC clearance.

Relationship between placental autophagy and inflammasome activities with morbidity of extremely preterm infants.

BACKGROUND: The placenta is the major regulatory element of the in-utero environment, and alterations in placental cellular functions in infection, inflammation, and hypoxemia lead to adverse preterm birth outcomes. The importance of regulation of autophagy and inflammasome activities has been shown in the pathogenesis of morbidities in immature animal models. This study aimed to determine the relationship between placental autophagy and inflammasome activities with morbidity in extremely preterm infants. METHODS: Premature infants born between 24th to 29th gestational weeks were evaluated prospectively. Placental LC3B and NLRP3 immunostainings were performed to assess autophagy and inflammasome activities. Preterm morbidities including respiratory distress syndrome (RDS), patent ductus ateriosus: (PDA), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), periventricular leukomalacia (PVL), sepsis, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP) and mortality were evaluated. RESULTS: Fifty-nine infants with a mean gestational age of 26.9 ± 1.5 weeks were included. Anti-LC3B staining scores were moderate or intense positive in 75% of the placentas. Anti-LC3B activity was not associated with the existance of evaluated neonatal morbidities or mortality. Autophagy and inflammasome coexistence were demonstrated in 35 placentas (59.3%). Anti-NLRP3 staining score was moderate or intensely positive in 75% of the placentas. Infants with BPD had a lower rate of positive anti -NLRP3 staining than infants without BPD (42.9 vs 57.1%, p=0.048). Infants who had hemodynamic significant patent ductus arteriosus (hsPDA) and surgical- NEC showed significantly intense anti-NLRP3 staining compared to infants who did not (18.8% vs 0%, p= 0.027 and 33% vs 7.5%, p=0.048 respectively). CONCLUSIONS: The results showed that autophagy and inflammatory activities were present in varying amounts in the placenta of preterm infants. Association of decreased or increased rates of inflammasome activities with certain diseases such as BPD, hsPDA and surgical-NEC indicates the role of the intrauterin inflammatory process and the importance of critical balance in inflammation. Because of the complex pathophysiology of preterm morbidities, placental autophagy and inflammasome activities seem worthy of further investigation.

Tumoral and Parenchymal Morphological Assessment in Liver Metastases of Colorectal Carcinoma: Micrometastasis, Peritumoral Lymphocytes, Tumor Budding and Differentiation are Potential Prognostic Factors.

Introduction: Various potential prognostic histopathologic factors for colorectal carcinoma liver metastasis have been proposed. However, there is still no consensus on pathological reporting of colorectal carcinoma liver metastasis resection materials. The aim of this study was to investigate the relation between selected tumoral and parenchymal histopathologic features and prognostic factors for better characterization and prognostic prediction of the patients with colorectal carcinoma liver metastasis. Methods: Hematoxylin-eosin stained slides from 100 patients who underwent hepatic resection were evaluated. Pathologic characteristics; including number of tumor nodules, largest tumor size, status of surgical margin, tumor distance to closest margin, tumor necrosis, the presence of tumor capsule, tumor differentiation, perineural and lymphovascular invasion, micrometastasis, tumor budding, peritumoral lymphocytic infiltrate and parenchymal features including steatosis, steatohepatitis, lobular inflammation, confluent necrosis, hepatocyte ballooning, portal inflammation were assessed. For 49 patients who were treated with preoperative chemotherapy, tumor regression grade and chemotherapy-related parenchymal changes such as sinusoidal damage, venous obstruction, nodular regenerative hyperplasia, steatosis and steatohepatitis were also evaluated. Results: The presence of lymphovascular invasion (p < 0.001), micrometastasis (p=0.004), absent or mild peritumoral lymphocytic infiltration (p =0.013), high tumor budding score (p=0.033) and moderate/poor differentiation (p=0.022) were significantly associated with shorter overall survival. Lymphovascular invasion (p < 0.001) was an independent predictor of mortality in multivariate analysis. Conclusions: We conclude that tumor differentiation, lymphovascular invasion, micrometastasis, peritumoral lymphocytic reaction and tumor budding score are potential prognostic histopathological features and candidates for inclusion in pathology reports of colorectal carcinoma liver metastasis resections.

The Site of Lymph Node Metastasis: A Significant Prognostic Factor in Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: While the presence and number of metastatic lymph nodes (LNs) are important prognostic factors for pancreatic ductal adenocarcinoma (PDAC), there is no recommendation to specify metastatic regional LN localization in the current staging system. The aim of this study was to evaluate the prognostic effect of regional metastatic LN localizations in PDAC. MATERIAL AND METHOD: Metastatic sites of 101 consecutive PDAC patients who underwent pancreaticoduodenectomy were classified as peripancreatic, perigastric, hepatica communis, hepatoduodenal, and superior mesenteric artery. The frequency of metastasis in each region and the association between the presence of metastasis in each site and overall and disease-free survival were statistically analyzed. RESULTS: Eighty cases (79.2%) had peripancreatic, 7 (6.9%) had perigastric, 6 (5.9%) had hepatica communis, 7 (6.9%) had hepatoduodenal, and 4 (4%) had superior mesenteric artery LN metastasis. The overall and disease-free survival values were significantly shorter in patients with hepatoduodenal LN metastasis (log rank; p= 0.001, p=0.017, respectively). The presence of metastatic superior mesenteric artery LN was significantly associated with shorter disease-free survival in univariate analysis (p=0.017). Hepatoduodenal LN metastasis was an independent predictor of mortality (p=0.005) in multivariate analysis. CONCLUSION: The presence of hepatoduodenal LN metastasis is an independent poor prognostic factor for mortality. The presence of metastatic LN in the superior mesenteric artery region was significantly associated with shorter disease-free survival time, although not an independent predictor. We conclude that the metastatic regional LN sites, especially the hepatoduodenal region, have an impact on the prognosis, and should be included in synoptic pathology reports.

Peritumoral histopathologic findings in patients with chronic viral hepatitis-associated hepatocellular carcinoma.

Data on peritumoral histopathologic findings in patients with hepatocellular carcinoma (HCC) is limited. In this retrospective study, we evaluated the peritumoral histopathologic changes in patients with chronic viral hepatitis (CVH)-associated HCC (CVH-HCC) and their prognostic value. 61 consecutive cirrhotic patients who underwent liver transplantation due to CVH-HCC were included. Histopathologic features within 1 cm distance of the tumor, and their association with clinicopathological characteristics and prognosis were evaluated. A random representative slide of cirrhotic parenchyma unrelated to invasive and/or dysplastic foci was also evaluated for the same histopathologic criteria. The majority (85%, n = 52) were male with a median age of 55 ± 6.38 (range, 39-67). The etiologic agent was only HBV in 90% (n = 55). The most common peritumoral findings were portal inflammation (100%; n = 61), ductular reaction (100%; n = 61) and sinusoidal dilatation (95%; n = 58). Macrovascular invasion was observed only in four cases (7%) with mild peritumoral portal inflammation. Neutrophilic infiltration of the peritumoral portal tracts (n = 18; 30%) was significantly associated with pT4 tumor stage, tumor grade, macrovascular invasion, and pretransplant therapy. Patients with moderate or severe peritumoral sinusoidal dilatation tended to have worse prognosis, albeit not significantly. Peritumoral ballooning degeneration was associated with multifocality, recurrence and recurrence-free survival in both uni- and multivariate analysis. Peritumoral histopathologic changes in CVH-HCC can be classified as: changes related to pathogenesis, changes indirectly affecting prognosis, and changes directly affecting prognosis. Peritumoral prominent ballooning degeneration may be a predictor of recurrence while portal neutrophilic infiltration and sinusoidal dilatation seem to indicate poor prognosis.

Reconsideration of Clinicopathologic Prognostic Factors in Pancreatic Neuroendocrine Tumors for Better Determination of Adverse Prognosis.

The question of how successful we are in predicting pancreatic neuroendocrine tumors (panNET) with poor prognosis has not been fully answered yet. The aim of this study was to investigate the effects of clinicopathological features on prognosis and to determine their validity in prediction of prognosis and whether a better prognostic classification can be made. Fifty-six patients who underwent pancreatic resection for pancreatic neuroendocrine tumor were included. The associations between clinicopathological parameters and prognosis were evaluated statistically. Efficiencies of different thresholds for tumor size, mitotic count, and Ki67 proliferation index for prognosis prediction were compared. Vascular invasion was statistically associated with high tumor grade, advanced pT stage, and mortality rate. The presence of non-functional tumor, lymphatic invasion, and > 10 cm tumor size were significantly related to shorter overall survival. Advanced pT stage (pT3-4), > 5 cm tumor size, and high tumor grade (grades 2-3) were significantly associated with shorter disease-free survival. The mortality rate showed the strongest statistical significance with mitotic count when grouped as 1: < 2, 2: 2-10, and 3: > 10 mitosis/ 2 mm2. The 10% threshold value for Ki67 index was more successful in predicting adverse prognosis. Among the morphologic variants, the ductulo-insular variant was the most promising to have positive prognostic value in our series, although no statistical significance was detected. In conclusion, threshold values of 5 cm and 10 cm for tumor size, 10% for Ki67 proliferation index, and 10/2 mm2 for mitotic count and vascular and lymphatic invasion assessed separately are potential prognostic candidates for better stratification of panNETs.

A Nobel-Winning Scientist: Aziz Sancar and the Impact of his Work on the Molecular Pathology of Neoplastic Diseases.

Aziz Sancar, Nobel Prize winning Turkish scientist, made several discoveries which had a major impact on molecular sciences, particularly disciplines that focus on carcinogenesis and cancer treatment, including molecular pathology. Cloning the photolyase gene, which was the initial step of his work on DNA repair mechanisms, discovery of the "Maxicell" method, explanation of the mechanism of nucleotide excision repair and transcription-coupled repair, discovery of "molecular matchmakers", and mapping human excision repair genes at single nucleotide resolution constitute his major research topics. Moreover, Sancar discovered the cryptochromes, the clock genes in humans, in 1998, and this discovery led to substantial progress in the understanding of the circadian clock and the introduction of the concept of "chrono-chemoterapy" for more effective therapy in cancer patients. This review focuses on Aziz Sancar's scientific studies and their reflections on molecular pathology of neoplastic diseases. While providing a new perspective for researchers working in the field of pathology and molecular pathology, this review is also an evidence of how basic sciences and clinical sciences complete each other.

How to Set Up a Molecular Pathology Lab: A Guide for Pathologists.

In today's pathology practice, pathologists combine molecular tests with conventional histopathological methods. Pathology laboratories should therefore be designed and operated in accordance with the requirements of molecular testing procedures. While the specifics of the requirements may vary depending on the spectrum of the tests that will be performed, there are several basic criteria that need to be fulfilled for standardization. Adequate space, appropriate equipment and qualified personnel are required to establish a molecular pathology laboratory. One of the most important points that should be taken into consideration while designing a molecular pathology laboratory is to create a plan to prevent contamination. As molecular diagnosis has a major role in treatment decisions, the management of the molecular pathology laboratory is of utmost importance. In this review, the criteria required to establish an optimal molecular pathology laboratory will be reviewed.

The Role of Log Odds of Positive Lymph Nodes in Predicting the Survival after Resection for Ampullary Adenocarcinoma.

Lymph node metastasis is a important factor on survival in ampullary adenocarcinoma. Log odds of positive lymph nodes (LODDS) is a novel prognostic indicator on lymph node status. We aimed to evaluate the prognostic impact of LODDS for the patients with ampullary adenocarcinoma who underwent R0 pancreaticoduodenectomy. The study includes 42 patients.. LODDS was calculated as "log (number of metastatic lymph nodes+0.5)/(number of total harvested nodes - metastatic lymph nodes+0.5)". LODDS subgroups were created based on their LODDS value: LODDS1(LODDS≤ - 1.5), LODDS2(-1.5 < LODDS≤ - 1.0), LODDS3(-1.0 < LODDS≤ - 0.5), LODDS4(LODDS> - 0.5). The mean survival time was 72.7 ± 7.82 months. Survival rates for 1, 3 and 5 years were 93%, 65% and 45%, respectively. The mean LODDS value was -1.0466 ± 0.51. LODDS subgroups show strong correlation with Overall Survival(OS). The mean survival were 114.8, 81.8, 56.6 and 25.6 months in LODDS subgroups 1, 2, 3 and 4, respectively (Log-rank; p = 0.002), in addition LOODS values shows correlation with perineural invasion and micro vascular invasion (p = 0.015 and p = 0.001 respectively). Findings in our patient group support the hypothesis that LODDS subgroups correlate with OS, and that value of LODDS has considerable role in prediction of OS as well.

Porcine Dermal Collagen Prevents Seroma Formation After Mastectomy and Axillary Dissection in Rats.

OBJECTIVE: Seroma occurs as a result of accumulation lymphovascular liquid in the dead space forming after tissue dissection. It is the most common complication after breast surgery. Collagens are the common component of extracellular matrix and have an important role in wound healing. In this study, we aimed to investigate the efficiency of the Porcine Dermal Collagen in preventing Seroma. MATERIALS AND METHODS: Eighteen young female Wistar rats were used and divided into three groups. Mastectomy and axillary dissection were performed in each group. No other procedures were performed in Group 1 (Control group). Porcine dermal collagen was applied to 50% of the mastectomy field in Group 2 and to 100% of the mastectomy field in Group 3. RESULTS: Seroma volume was significantly decreased in Group 3 in contrast to Groups 1 and 2 (p<0.001) and in Group 2 in contrast to Group 1 (p<0.001). Vascular proliferation, granulation tissue formation and congestion were significantly increased in Group 3 (p<0.05). CONCLUSION: We conclude that the use of Porcine Dermal Collagen reduces the formation of seroma in the model of experimental mastectomy and axillary dissection. As the amount of Porcine Dermal Collagen applied increases the formation of seroma reduces.

SATB2 Expression Distinguishes Ovarian Metastases of Colorectal and Appendiceal Origin From Primary Ovarian Tumors of Mucinous or Endometrioid Type.

The primary origin of some ovarian mucinous tumors may be challenging to determine, because some metastases of extraovarian origin may exhibit gross, microscopic, and immunohistochemical features that are shared by some primary ovarian mucinous tumors. Metastases of primary colorectal, appendiceal, gastric, pancreatic, and endocervical adenocarcinomas may simulate primary ovarian mucinous cystadenoma, mucinous borderline tumor, or mucinous adenocarcinoma. Recently, immunohistochemical expression of SATB2, a transcriptional regulator involved in osteoblastic and neuronal differentiation, has been shown to be a highly sensitive marker of normal colorectal epithelium and of colorectal adenocarcinoma. SATB2 expression has not been reported in normal epithelium of the female reproductive tract. Therefore, we hypothesized that SATB2 may be of value in distinguishing ovarian metastases of colorectal adenocarcinoma from primary ovarian mucinous tumors and from primary ovarian endometrioid tumors. Among primary ovarian tumors, SATB2 staining was observed in 0/22 mucinous cystadenomas that lacked a component of mature teratoma, 4/12 mucinous cystadenomas with mature teratoma, 1/60 mucinous borderline tumors, 0/17 mucinous adenocarcinomas, 0/3 endometrioid borderline tumors, and 0/72 endometrioid adenocarcinomas. Among ovarian metastases, SATB2 staining was observed in 24/32 (75%) colorectal adenocarcinomas; 8/10 (80%) low-grade appendiceal mucinous neoplasms; and 4/4 (100%) high-grade appendiceal adenocarcinomas. No SATB2 staining was observed in any ovarian metastasis of pancreatic, gastric, gallbladder, or endocervical origin. Evaluation of primary extraovarian tumors showed the highest incidences of SATB2 staining among primary colorectal adenocarcinomas (71%), primary appendiceal low-grade mucinous neoplasms (100%), and primary appendiceal high-grade adenocarcinomas (100%). Similar to their metastatic counterparts, none of the primary pancreatic or gastric adenocarcinomas showed any SATB2 staining. In a subset of tumors for which CK7, CK20, and CDX2 were available, SATB2 was never positive in any tumor of any origin that was CK7+CK20-CDX2-. Among tumors that coexpressed all 3 markers (CK7+CK20+CDX2+), 6/7 SATB2 tumors were of colorectal or appendiceal origin, and 1/7 was a primary ovarian borderline tumor. We conclude that ovarian tumors with mucinous or endometrioid features that express SATB2 are unlikely to be of primary ovarian origin unless there is a component of mature teratoma in the ovary; instead, attention should be directed to a colorectal or appendiceal origin. SATB2 may be of particular value in ovarian mucinous tumors that are positive for all 3 markers (CK7+CK20+CDX2+), as SATB2 staining strongly implicates a colorectal or appendiceal origin.

Pleuropulmonary blastoma: a case report.

Pleuropulmonary blastoma is rare embryonal tumor of infancy and early childhood and it often arises from lung and more rarely from the parietal pleura. We present this entity which has no systematic data associated with its incidence in order to discuss clinical, histopathological, immunohistochemical features and the differential diagnosis. A three-year-old boy presented with fever showed signs of upper respiratory tract infection. Radiological examination revealed a solid mass filling the right hemithorax. The patient underwent core needle biopsy, wedge biopsy and lobectomy. Biopsy and surgical material were examined histopathologically. The tumor was composed of predominantly solid areas consisting blastemal cells with spindle, polygonal and round nuclei in the myxoid stroma. Immunohistochemical staining of the tumor cells were positive with vimentin and desmin. MIB-1 labeling index was above 90%. Histological diagnosis was pleuropulmonary blastoma type 3. The surgically sampled adjacent diafragma was also infiltrated with the tumor. The patient was treated with chemotherapy and showed no signs of recurrence in the follow-up of 9 months. Pleuropulmonary blastoma is a very rare childhood cancer that needs to be kept in mind in the pathological differential diagnosis of thoracic tumors in the children.

Transitional cell-like morphology in ovarian endometrioid carcinoma: morphologic, immunohistochemical, and behavioral features distinguishing it from high-grade serous carcinoma.

Transitional cell-like growth has been reported as a morphologic variant of endometrioid adenocarcinoma in the uterus but is not well-described in the ovary. We report the clinicopathologic features of a series of ovarian endometrioid adenocarcinomas with transitional cell-like morphology, emphasizing the distinction from its mimics, including high-grade serous carcinoma, transitional cell carcinoma, and granulosa cell tumor. Among a cohort of 71 ovarian endometrioid adenocarcinomas surgically staged at our institution, 10 tumors (14%) exhibited transitional cell-like morphology. Patient age ranged from 39 to 79 years (mean, 52 y). Five tumors were stage I, 2 were stage II, and 3 stage III. The tumors ranged from 8.5 to 23 cm, and the transitional cell-like component occupied from 5% to 90% of the overall tumor, with the remainder being conventional endometrioid adenocarcinoma. The most compelling findings to support that this tumor pattern represents a morphologic variant of endometrioid adenocarcinoma are that the transitional cell-like components (1) merged directly and seamlessly with the conventional endometrioid component; (2) contained areas of mature or immature squamous differentiation; (3) lacked WT1 immunoexpression; (4) lacked the characteristic p53/p16 immunophenotype of high-grade serous carcinoma; and (5) did not appear to independently affect patient outcome. Two patients (20%) whose tumor contained transitional cell-like morphology died, whereas 14 patients (23%) lacking this morphology died. Although uncommon, transitional cell-like morphology appears to be a variant growth pattern of ovarian endometrioid adenocarcinoma that does not affect behavior and that should be distinguished from high-grade serous carcinoma and conventional ovarian transitional cell carcinoma.

Pleuropulmonary Blastoma: A Case Report.

Pleuropulmonary blastoma is rare embryonal tumor of infancy and early childhood and it often arises from lung and more rarely from the parietal pleura. We present this entity which has no systematic data associated with its incidence in order to discuss clinical, histopathological, immunohistochemical features and the differential diagnosis. A three-year-old boy presented with fever showed signs of upper respiratory tract infection. Radiological examination revealed a solid mass filling the right hemithorax. The patient underwent core needle biopsy, wedge biopsy and lobectomy. Biopsy and surgical material were examined histopathologically. The tumor was composed of predominantly solid areas consisting blastemal cells with spindle, polygonal and round nuclei in the myxoid stroma. Immunohistochemical staining of the tumor cells were positive with vimentin and desmin. MIB-1 labeling index was above 90%. Histological diagnosis was pleuropulmonary blastoma type 3. The surgically sampled adjacent diafragma was also infiltrated with the tumor. The patient was treated with chemotherapy and showed no signs of recurrence in the follow-up of 9 months. Pleuropulmonary blastoma is a very rare childhood cancer that needs to be kept in mind in the pathological differential diagnosis of thoracic tumors in the children.

Ovarian endometrioid adenocarcinoma: incidence and clinical significance of the morphologic and immunohistochemical markers of mismatch repair protein defects and tumor microsatellite instability.

A subset of women with uterine cancer exhibiting defective mismatch repair (MMR) proteins and microsatellite instability (MSI) may have Lynch syndrome, which also confers a risk for colorectal cancer and other cancers in the patient and in her family. Screening algorithms based on clinical and pathologic criteria are effective in determining which patients with uterine cancer are most likely to benefit from definitive genetic testing for Lynch syndrome. Ovarian cancer, particularly endometrioid adenocarcinoma, is also associated with Lynch syndrome, although the risk is much smaller than for uterine cancer. This study evaluated whether the morphologic criteria [tumor-infiltrating lymphocytes (TILs), peritumoral lymphocytes (PTLs), dedifferentiated morphology)] currently used to screen uterine cancer for further Lynch syndrome testing can be applied to ovarian cancer. Among 71 patients with pure ovarian endometrioid adenocarcinoma treated at a single institution, 13% had a tumor with TILs, 3% had PTLs, and none had dedifferentiated morphology. Overall, 10% of tumors had abnormal MMR protein status, defined as complete immunohistochemical loss of expression of MLH1, MSH2, MSH6, and/or PMS2. Each of these tumors with abnormal MMR status demonstrated MSI using a polymerase chain reaction-based assay evaluating 5 mononucleotide repeat markers. No relationship was found between patient age, TILs, PTLs, or a spectrum of other morphologic variables and MMR protein status/MSI. Only 1/7 tumors with abnormal MMR/MSI had TILs/PTLs. Among 14 patients who died, 12 (86%) had normal MMR status. Among 7 patients with tumors with abnormal MMR/MSI, 5 (71%) were alive without disease. Concurrent uterine tumor was present in 5/7 patients whose ovarian tumor had abnormal MMR/MSI. This study suggests that the morphologic criteria used to screen patients with uterine cancer for further Lynch syndrome testing are not applicable in patients with ovarian cancer. Although abnormal MMR/MSI did not carry prognostic value in this study, it did predict the involvement of the uterus by the tumor. Thus, in patients with ovarian endometrioid adenocarcinoma who undergo uterus-sparing surgery, abnormal MMR/MSI should prompt further diagnostic evaluation of the endometrium for tumor.

Does glucagon like peptide-2 receptor expression have any effect on the development of human colorectal cancer?

BACKGROUND/AIMS: Glucagon like peptide-2 may play an important role in human colon cancer and polyp development because of its proliferative and antiapopitotic effects especially in colon. In this study, we investigated the role of human glucagon like peptide and it's receptor in development of human colorectal carcinogenesis. MATERIAL AND METHODS: The study includes 30 patients in colon cancer group and 20 patients in colonic polyp group who have been diagnosed by endoscopic and pathologic examination in Dokuz Eylül University, Department of Gastroenterology within 2 year-period. For comparison biopsies were taken from normal appearing colonic mucosa of the same patient. The cancer, polyp and normal colon mucosa samples were stained with glucagon like peptide receptor antibody by immunohistochemical method. RESULTS: Glucagon like peptide 2 receptor positivity of colon cancer patients was 20 % (6/30) in focal cytoplasmic coloration while it was 0 % in colonic adenomas and 100 % in enteroendocrine cells of normal colonic mucosa. Statistically significant differences were found by the comparison of colonic polyp and normal colonic tissue (p=0.000), colonic cancer and normal colonic tissue (p=0.000) and colonic polyp and cancer tissues (p= 0.023). CONCLUSION: Glucagon like peptide-2 receptor expression in colonic adenomas was not detected in human in contrary to the study on mice. Our study suggested that Glucagon like peptide-2 receptor expression is not a factor in adenoma-cancer pathogenesis. More studies are needed on this subject with more facts and different methods.