CD133, CD47, and PD-L1 Expression in Ovarian High-grade Serous Carcinoma and Its Association with Metastatic Disease: A Cross-sectional Study.

INTRODUCTION: Ovarian cancer is a primary cause of cancer-related death in women. At the time of diagnosis, the majority of ovarian malignancies had metastasized. It is believed that cancer stem cells (CSCs) and immune evasion play a crucial role in the metastatic process. The objective of this study was to describe the expression profiles of cluster of differentiation (CD)133, CD47, and programmed death ligand 1 (PD-L1) in high-grade serous ovarian cancer (HGSC) as commonly utilized markers for CSCs and immune evasion. MATERIAL AND METHODS: Using an immunohistochemical procedure, 51 HGSC tissue samples were stained with anti-CD133, anti-CD47, and anti-PDL1 antibodies. The samples contained 31 HGSC with metastases and 20 HGSC absent metastases. The expression of CD133, CD47, and PD-L1 was compared between groups. RESULTS: Strong expression of CD133 and CD47 was seen in 52% and 66% of tissue samples, respectively. Twenty of the thirty-one patients with metastases had a significant level of CD133 expression, with a p-value of 0.039. CD47 expression was increased in 26 of 31 samples with metastatic disease. A 62.7 percent of samples were negative for PD-L1 expression, significantly inversely correlated with HGSC metastatic disease (p=0.023). Although there was no significant association between CD133, CD47, or PD-L1 expression and age, Tumor Infiltrating Lymphocytes demonstrated a significantly varied relationship. CONCLUSION: Our findings suggested that expression of CD133, CD47, and PD-L1 may have dynamically increased as the primary lesion progressed to the metastatic lesion, implying that these proteins may be involved in the progression of high-grade serous ovarian cancer from the primary to the metastatic stage.

A rare nasal fibrosarcoma: A case report.

INTRODUCTION: Fibrosarcoma is a malignant neoplasm, with nasal localization uncommon. Clinically, the main symptoms are epistaxis and nasal obstruction. Microscopically, it is characterized by a dense proliferation of fibroblasts with a herringbone pattern and spindle-shaped cells with hyperchromatic nuclei. PRESENTATION OF CASE: We report a nasal fibrosarcoma of a 37-year-old woman with a recurrent history of epistaxis and nasal obstruction for several years. A biopsy was performed, and the histopathological findings reported a dense proliferation of fibroblasts with a herringbone pattern and spindle-shaped cells with hyperchromatic nuclei. The immunohistochemistry was positive for Ki67, P53, and vimentin staining. The final diagnosis was nasal fibrosarcoma. The patient underwent functional endoscopic sinus surgery and extirpation of the tumor on the wall of the right maxilla, right ethmoid sinus, and right frontal area. Thirteen months later, the patient experienced a recurrence. An external approach was taken under general anesthesia via lateral rhinotomy with medial maxillectomy. The patient underwent chemotherapy with a regimen of paclitaxel and cisplatin for six cycles. DISCUSSION: We gave chemotherapy in this case because the patient experienced a recurrence, tumor-free margins were not obtained, and a computed tomography scan showed bone involvement. CONCLUSION: Nasal fibrosarcoma is a rare malignant neoplasm, which can be diagnosed by its histopathological features and immunohistochemistry.

Risk-stratification machine learning model using demographic factors, gynaecological symptoms and ß-catenin for endometrial hyperplasia and carcinoma: a cross-sectional study.

BACKGROUND: Demographic features, suggestive gynaecological symptoms, and immunohistochemical expression of endometrial ß-catenin have a prognostic capacity for endometrial hyperplasia and carcinoma. This study assessed the interaction of all variables and developed risk stratification for endometrial hyperplasia and carcinoma. METHODS: This cross-sectional study was conducted from January 2023 to July 2023 at two teaching hospitals in Makassar Indonesia. Patients (< 70 years old) with suggestive symptoms of endometrial hyperplasia or carcinoma or being referred with disease code N.85 who underwent curettage and/or surgery for pathology assessment except those receiving radiotherapy, or chemotherapy, presence of another carcinoma, coagulation disorder, and history of anti-inflammatory drug use and unreadable samples. Demographic, and clinical symptoms were collected from medical records. Immunohistochemistry staining using mouse-monoclonal antibodies determined the ß-catenin expression (percentage, intensity, and H-score) in endometrial tissues. Ordinal and Binary Logistic regression identified the potential predictors to be included in neural networks and decision tree models of histopathological grading according to the World Health Organization/WHO grading classification. RESULTS: Abdominal enlargement was associated with worse pathological grading (adjusted odds ratio/aOR 6.7 95% CI 1.8-24.8). Increasing age (aOR 1.1 95% CI 1.03-1.2) and uterus bleeding (aOR 5.3 95% CI 1.3-21.6) were associated with carcinoma but not with %ß-catenin and H-Score. However, adjusted by vaginal bleeding and body mass index, lower %ß-catenin (aOR 1.03 95% 1.01-1.05) was associated with non-atypical hyperplasia, as well as H-Score (aOR 1.01 95% CI 1.01-1.02). Neural networks and Decision tree risk stratification showed a sensitivity of 80-94.8% and a specificity of 40.6-60% in differentiating non-atypical from atypical and carcinoma. A cutoff of 55% ß-catenin area and H-Score of 110, along with other predictors could distinguish non-atypical samples from atypical and carcinoma. CONCLUSION: Risk stratification based on demographics, clinical symptoms, and ß-catenin possesses a good performance in differentiating non-atypical hyperplasia with later stages.

Primary leiomyosarcoma of the breast: A case report and literature review.

INTRODUCTION: Primary leiomyosarcoma is an uncommon form of stromal breast sarcoma. Approximately 73 cases have been documented in English-language literature to date. To our knowledge, this is the first report from Indonesia of an adolescent female with primary leiomyosarcoma of the breast. CASE PRESENTATION: A 30-year-old Southeast Asian female presented with a tumor in her left breast. Clinical examination revealed a 12 × 8-centimeter tumor. The supraclavicular, subclavicular, and axillary lymphadenopathy were not palpable. An ultrasound revealed a Breast Imaging Reporting and Data System category 5. Abdominal ultrasonography and chest x-ray were normal, as were blood chemistry and routine blood tests. A wide excision with a surgical margin of 2 cm was performed. Pathological investigation identified the mass as a leiomyosarcoma. The pelvis, abdomen, and lung CT scan metastatic workups were negative. The patient is well 8 months post-surgery, with no signs of recurrence. CLINICAL DISCUSSION: Wide local excision has been the mainstay of treatment for leiomyosarcoma; however, there is no accepted standard of treatment due to the rarity of the disease. CONCLUSION: Breast leiomyosarcomas have a more favorable prognosis than other breast neoplasms; however, patients must be closely monitored for recurrence or metastases. While there are no known predictors of outcomes, the margins of the initial surgery, mitotic activity, and atypia cellularity are more indicative of malignancy.

Prognostic Value of ß-Catenin and L1CAM Expressions in Type I Endometrial Carcinoma.

OBJECTIVE: The aim of this study is to evaluate the expression of ß-catenin and L1CAM in the type I of Endometrial Carcinoma. MATERIAL AND METHODS: This study was an analytical study with a cross-sectional design using 49 samples of type I Endometrial Carcinoma. Immunohistochemical method was used to evaluate the expression of ß-catenin and L1CAM related to two significant prognostic parameters i.e., lymphovascular space invasion (LVSI) and metastases event of type I Endometrial Carcinoma samples. RESULTS: From all samples collected, based on the presence of LVSI, there were 17 cases (34.7%) with LVSI and 32 (65.3%) no LVSI. Among them, there were 13 cases that included lymph node or omental samples in type I Endometrial Carcinoma, 5 (38.5%) cases of metastasis, and 8 (61.5%) cases that did not metastasize. The statistical results showed that there was a significant correlation between ß-catenin and L1CAM expressions examined from tumor cells with lymphovascular space invasion and the presence of metastases in the type I Endometrial Carcinoma (p <0.05). CONCLUSION: This study suggest that the positive expression of ß-catenin together with L1CAM can participate in the development of tumor cells in type I Endometrial Carcinoma, in its ability to involve lymphovascular space invasion, and metastases to other sites. Our results indicate that both of ß-catenin and L1CAM are prominent biomarkers for the prognosis of type I Endometrial Carcinoma.

Analysis of mRNA and protein kidney injury Molecule-1 (KIM-1) expression in a kidney model during the initiation phase of ischemia reperfusion injury.

BACKGROUND: Kidney injury molecule-1 (KIM-1) is a transmembrane glycoprotein expressed predominantly on the proximal tubular epithelium. OBJECTIVE: We wanted to see if there was a critical time for increased tubular damage and its related biomarker, KIM-1 mRNA, and protein expressions during the first 24 h of ischemia-reperfusion injury. METHOD: An Experimental research used five male Rattus Norvegicus rats in each group. Bulldog clamp was used to clamp renal arteries and veins to create renal ischemia. Immunohistochemistry was used for the analysis of KIM-1 protein expression. While Tubular Injury Score was examined by Histopathology. RT-PCR was used for KIM-1 mRNA expression. RESULTS: Tubular Injury Score (TIS) was significantly higher in ischemia than control. TIS remained similar after IR 30 min, peaked at IR 2 h, and decreased to the level of IR 30 min at IR 24 h.The KIM-1 mRNA expression was also higher in ischemia than in control. Similarly, KIM-1 mRNA expression increased more after IR 30 min, IR 2 h, and IR 24 h.The KIM-1 protein expression was higher in ischemia than in control. KIM-1 protein increased more after IR 30 min, IR for 2 h, and remained similar at IR for 24 h.KIM-1 mRNA and protein expressions at IR 2 h were significantly different compared to ischemia but not significantly different compared to that in IR 24 h. CONCLUSIONS: KIM-1 mRNA and protein expressions increased within 24 h IR with the critical time was in the 2 h IR.

Prediction of hereditary nonpolyposis colorectal cancer using mRNA MSH2 quantitative and the correlation with nonmodifiable factor.

BACKGROUND: Hereditary non-polyposis colon cancer is a dominantly inherited syndrome of colorectal cancer (CRC), with heightened risk for younger population. Previous studies link its susceptibility to the DNA sequence polymorphism along with Amsterdam and Bethesda criteria. However, those fail in term of applicability. AIM: To determine a clear cut-off of MSH2 gene expression for CRC heredity grouping factor. Further, the study also aims to examine the association of risk factors to the CRC heredity. METHODS: The cross-sectional study observed 71 respondents from May 2018 to December 2019 in determining the CRC hereditary status through MSH2 mRNA expression using reverse transcription-polymerase chain reaction and the disease's risk factors. Data were analyzed through Chi-Square, Fischer exact, t-test, Mann-Whitney, and multiple logistics. RESULTS: There are significant differences of MSH2 within CRC group among tissue and blood; yet, negative for significance between groups. Through the blood gene expression fifth percentile, the hereditary CRC cut-off is 11059 fc, dividing the 40 CRC respondents to 32.5% with hereditary CRC. Significant risk factors include age, family history, and staging. Nonetheless, after multivariate control, age is just a confounder. Further, the study develops a probability equation with area under the curve 82.2%. CONCLUSION: Numerous factors have significant relations to heredity of CRC patients. However, true important factors are staging and family history, while age and others are confounders. The study also established a definite cut-off point for heredity CRC based on mRNA MSH2 expression, 11059 fc. These findings shall act as concrete foundations on further risk factors and/or genetical CRC future studies.

CD133 Act as an Essential Marker in Ovarian Carcinogenesis.

OBJECTIVE: To analyze the role of cancer stem cells (CSC) in ovarian carcinogenesis through the identification of CD133 expression in the normal ovary (NO), serous cystadenoma (SC), borderline serous tumour (BST), low-grade serous carcinoma (LGSC), and high-grade serous carcinoma (HGSC). MATERIALS AND METHODS: A total of 48 tissue samples contain 5 NO, 10 SC, 5 BST, 8 LGSC, and 20 HGSC were stained with anti-CD133 antibody by immunohistochemical protocol. The difference in the H-score of CD133 expression between groups and their relationship to age, histomorphology, and localization was analyzed. RESULTS: CD133 expression varied among tumor groups, with clinicopathologic parameters showing diverse associations (age p = 0.773; histomorphology p = 0.001; and localization p = 0.026). The comparison of CD133 H-scores differed significantly between each group (p = 0.0031), in which precursor and malignant lesions possessed more robust CD133 expression. CONCLUSION: The presence of CD133 cellular expression and localization in different types of serous ovarian tumours suggests that these markers are involved in ovarian tumorigenesis.

The value of tumor-infiltrating lymphocytes and CD8 expression as a predictor of response to anthracycline-based neoadjuvant chemotherapy in invasive breast carcinoma of no special type.

BACKGROUND: The immune system is known to play an important role in tumor cell eradication. Although cancer cells were able to escape from the immune system, many studies showed mononuclear inflammatory cell infiltrates known as tumor-infiltrating lymphocytes (TILs) on breast cancer histopathology specimens showed better prognosis, including in disease-free survival (DFS) and chemotherapy responses. OBJECTIVE: This study aimed to reveal the predictive value of tumor-infiltrating lymphocytes (TILs) levels and CD8 expression in invasive breast carcinoma of no special type patients' samples on response to anthracycline-based neoadjuvant chemotherapy. METHODS: 75 pre-treatment biopsy samples that were diagnosed as invasive breast carcinoma of no special type were evaluated. TILs level determined following recommendations of International TILs Working Group 2014, CD8 expression assessed semiquantitatively after immunohistochemistry staining. Response to anthracycline-based neoadjuvant chemotherapy evaluated clinically using Response Evaluation Criteria in Solid Tumours (RECIST) criteria and pathologically by evaluating hematoxylin and eosin (H&E)-stained slides from mastectomy specimens after 3 or 4 cycles of neoadjuvant chemotherapy. RESULTS: Chi-squared analysis showed a significant relationship between TILs level and CD8 expression with chemotherapy responses clinically (p = 0.011 and p = 0.017 respectively) but not pathologically. Furthermore, the logistic regression test exhibit the predictive value of TILs level was 66.7% and CD8 expression was 64%. CONCLUSIONS: This study results suggest that TILs level and CD8 expression may be added as predictive factors to the response of anthracycline-based neoadjuvant chemotherapy, and oncologists may take benefit in breast cancer patient's management.

Effects of propolis and its bioactive components on breast cancer cell pathways and the molecular mechanisms involved.

BACKGROUND: Breast cancer is a female malignancy that is a significant cause of mortality worldwide. Currently, investigations on natural ingredients as new candidates for chemopreventive agents and breast cancer chemotherapies are increasing. Propolis is a natural resinous material produced by honeybees that exhibit anticancer potential. Several studies have mentioned the major bioactive compounds of propolis, but their mechanism of action is not clearly understood. OBJECTIVES: The purpose of this review is to collect and summarize the evidence related to the effectiveness of propolis and its bioactive contents as candidates for breast cancer therapy and analyze the molecular mechanisms involved in their therapeutic pathways. METHODS: We reviewed 94 articles from journals and databases, extracted the results, and produced summaries and conclusions. RESULTS: Propolis and its bioactive ingredients show cytotoxic, anti-proliferative, pro-autophagic, anti-metastatic, and antioxidant activities, as well as synergistic effects with chemotherapy or radiotherapy in breast cancer. Its therapeutic activity involves various target molecules, including NF-κß, Fas receptors, p53, TLR4, ANXA7, and voltage-gated Na+ channel (VGSC). CONCLUSION: The bioactive components of propolis and the target molecules involved need to be explored further to develop new breast cancer therapies and overcome the problem of chemoradiation resistance.

Gata-3 and KI-67 expression in correlation with molecular subtypes of breast cancer.

OBJECTIVES: This study aims to evaluate and compare four breast cancer subtypes defined by immunohistochemistry expression of ER, PR, and HER-2 in correlation with Ki-67 and GATA-3 expression. METHODS: Slides from 89 paraffin blocks of invasive breast cancer patients with four molecular subtypes based on HER-2, ER, and PR expression were then stained with Ki-67 and GATA-3 antibodies to evaluate their expression in correlation with molecular subtype and metastases to lymph nodes. RESULTS: This study was a retrospective study of 89 invasive breast cancers. Luminal A; Luminal B; HER2+; and triple-negative types were 35 (39.3%), 10 (11.2%), 27 (30.3%), and 17 (19.1%) samples. Expression of Ki-67 was increased in triple-negative (TN) tumor compared to non-triple-negative (non-TN) tumor subtypes (p < 0.05). This Ki-67 expression was inversely correlated with the positivity of hormone receptor expression related to lymph-node metastases in TN-type tumors. Sixty-two (57%) samples were immunohistochemically positive for GATA-3. GATA-3 positive samples were significantly more likely to be ER and PR-positive, Ki-67 negative, and luminal A tumors. CONCLUSIONS: Subtype triple-negative breast cancer correlates with high expression of Ki-67 that contributes to poor prognosis of this subtype. The higher Ki-67 expression was correlated with the absence of hormone receptor expression compared with the negativity of Her-2 expression, downplay a role in nodal metastases in a triple-negative tumor. GATA-3 positive breast cancer showed luminal differentiation characterized by high ER expression and mainly was classified as luminal A type tumor with a better prognosis.

The Role of microRNAs in the Cisplatin- and Radio-Resistance of Cervical Cancer.

Cervical cancer is the fourth leading cause of cancer-related death among women worldwide. The chemotherapeutical agent cisplatin, a small platinum-based compound, is considered as the standard therapy for locally advanced cervical cancer or recurrent cancers, sometimes in combination with radiotherapy or other drugs. However, drug resistance and radio-resistance phenomena could reduce the life expectancy of cervical cancer patients. Resistance mechanisms are complex and often involve multiple cellular pathways in which microRNAs (miRNAs) play a fundamental role. miRNAs are a class of endogenous non-coding small RNAs responsible for post-transcriptional gene regulation. Convincing evidence demonstrates that several deregulated miRNAs are important regulators in the onset of drug and radioresistance in cervical cancer, thus underlying their potential applications in a clinical setting. In this review, we summarized the mechanisms by which miRNAs affect both cisplatin and radioresistance in cervical cancer. We also described the regulatory loops between miRNAs and lncRNAs promoting drug resistance. Besides, we reported evidence for the role of miRNAs in sensitizing cancer cells to cisplatin-based chemotherapy, and provided some suggestions for the development of new combined therapies for cervical cancer.

Peutz-Jeghers syndrome in a woman presenting as intussusception: A case report.

INTRODUCTION: Peutz-Jeghers syndrome (PJS) is an uncommon autosomal dominant syndrome with a variable to high penetrance that leads to the development of polyps within the gastrointestinal mucosa. Here we report a case of an adult female suffering jejunoileal intussusception due to PJS. PRESENTATION OF CASE: A 30-year-old woman came to an emergency department with a small bowel obstruction caused by intussusception. The patient underwent an emergency exploratory laparotomy. An intussusception at the level of 60 cm from the ligamentum treitz was revealed, and the intussusception small bowel segment was not viable; we decided to perform segmental jejunoileal resection with the Bishop-Koop procedure, and the specimen histopathology of the segmental jejunoileal resection showed a typical hamartomatous polyp features. Two month later, diagnostic endoscopy showed multiple polyps (between 5 and 15 mm) in the large bowel. The polyps were removed with endoscopic polypectomy and examined histopathologically, showing characteristics of PJS. Further detailed family history was obtained, and similar skin lesions were detected on our patient's child (since birth). Although endoscopy screening identified multiple polyps in the child's ileum and large bowel, he was not suffering from abdominal symptoms. CONCLUSION: In patients with intussusception at a young age, PJS can be caused by the presence of a hamartoma polyp as a trigger for intussusception. If there are multiple polyps found in the gastrointestinal mucosa and other pathognomonic signs are found, such as hyperdense macular lesions on the lip and buccal mucosa, such cases should be confirmed as PJS.

Programmed death-ligand 1 expression and tumor-infiltrating lymphocytes in colorectal adenocarcinoma.

BACKGROUND: Programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) are considered have a prognostic value in several malignancies. This study investigated the correlation between PD-L1 expression of tumor cells with the degree of stromal TILs in colorectal adenocarcinoma. METHODS: A cross sectional study design performed by taking 52 colorectal adenocarcinoma samples. The specimens were stained by immunohistochemical procedure using PD-L1 rabbit monoclonal antibody and the degrees of TILs were assessed base on hematoxylin and eosin (H&E) staining. RESULTS: From a total of 52 samples, the positive PD-L1 expression of tumor cells were 44 (84.6%) samples with 22 (50.0%), 18 (40.9%) and 4 (9.1%) samples had low-, moderate-, and high-degree TILs, respectively. While the negative PD-L1 expression were eight (15.4%) samples with 1 (12.5%), three (37.5%) and four (50.0%) samples had low-, moderate-, and high-degree TILs, respectively. A value of P=0.017 (P<0.05) was obtained by the Chi-square test. CONCLUSIONS: This study concluded that there was a significant correlation between PD-L1 expression of tumor cells and the degree of TILs in colorectal adenocarcinoma. This result indicated that the degree of TILs had the potential to be used as a predictive factor for PD-L1 expression of tumor cells in colorectal adenocarcinoma.

The Crosstalk between Tumor Cells and the Microenvironment in Hepatocellular Carcinoma: The Role of Exosomal microRNAs and their Clinical Implications.

The communication between hepatocellular carcinoma (HCC) cells and their microenvironment is an essential mechanism supporting or preventing tumor development and progression. Recent evidence has identified extracellular vesicles (EVs) as one of the mechanisms mediating paracrine signaling between cells. Exosomes, the most described class of EVs, deliver proteins, mRNAs, noncoding RNAs, DNA, and lipids to recipient cells, also at remote distances. MicroRNAs (miRNAs), as part of the non-coding RNA exosomal cargo, have an important role in regulating cellular pathways in targeted cells, regulating several processes related to tumor progression invasion and metastasis, such as angiogenesis, immune-escape, epithelial-to-mesenchymal transition, invasion, and multi-drug resistance. Accumulating evidence suggests exosomal miRNAs as relevant players in the dynamic crosstalk among cancerous, immune, and stromal cells in establishing the tumorigenic microenvironment. In addition, they sustain the metastasic niche formation at distant sites. In this review, we summarized the recent findings on the role of the exosome-derived miRNAs in the cross-communication between tumor cells and different hepatic resident cells, with a focus on the molecular mechanisms responsible for the cell re-programming. In addition, we describe the clinical implication derived from the exosomal miRNA-driven immunomodulation to the current immunotherapy strategies and the molecular aspects influencing the resistance to therapeutic agents.

L1CAM Expression is Related to Non-Endometrioid Histology, and Prognostic for Poor Outcome in Endometrioid Endometrial Carcinoma.

The majority of endometrial carcinomas are classified as Type I endometrioid endometrial carcinomas (EECs) and have a good prognosis. Type II non-endometrioid endometrial carcinomas (NEECs) have a significant worse outcome. Yet, 20 % of the EECs are associated with an unexplained poor outcome. The aim of this study was to determine if L1CAM expression, a recently reported biomarker for aggressive tumor behavior in endometrial carcinoma, was associated with clinicopathological features of EECs. A total of 103 patients diagnosed as EEC at the Radboud University Medical Centre, based on the pathology report were selected. L1CAM status of these tumors was determined, and histologic slides were reviewed by two expert pathologists. L1CAM-positivity was observed in 17 % (18/103). Review of the diagnostic slides revealed that 11 out of these 18 L1CAM-positive tumors (61 %) contained a serous- or mixed carcinoma component that was not initially mentioned in the pathology report. L1CAM-expression was associated with advanced age, poor tumor grade, and lymphovascular space invasion. A worse five year progression free survival rate was observed for patients with L1CAM-positive tumors (55.6 % for the L1CAM-positive group, compared to 83.3 % for the L1CAM-negative group P = 0.01). L1CAM expression carries prognostic value for histologically classified EEC and supports the identification of tumors with a NEEC component.

High prevalence of atypical hyperplasia in the endometrium of patients with epithelial ovarian cancer.

OBJECTIVES: The aim of the present study is to determine the prevalence of endometrial premalignancies in women diagnosed with epithelial ovarian cancer (EOC). METHODS: Endometrial and ovarian specimens of 186 patients with EOC were retrospectively selected using the nationwide pathology network and registry, and sections were comprehensively reviewed: 136 (73%) serous, 19 (10%) endometrioid, 15 (8%) mucinous, seven (4%) clear cell, and nine (5%) undifferentiated. Immunohistochemical phenotypes were compared for patients with serous EOC with concurrent endometrial pathology. RESULTS: In 31%, endometrial (pre)malignancy was found: carcinoma in 3%, endometrial intraepithelial carcinoma (EIC) in 4%, and atypical hyperplasia in 24%. Atypical hyperplasia was found in 47% of endometrioid EOCs but in 7% to 33% of other subtypes. Body mass index was higher concurrent to atypical hyperplasia (P=.001). Serous EOC and EIC immunophenotypes were comparable, whereas atypical hyperplasia was expressed differently. CONCLUSIONS: Apart from synchronous endometrial carcinoma, endometrial premalignancies should be taken into account when determining optimal treatment for women diagnosed with EOC.

Evidence for the antagonistic form of CXC-motif chemokine CXCL10 in serous epithelial ovarian tumours.

Patients with high-grade, serous epithelial ovarian carcinoma (HGSOC) are generally diagnosed with extensive peritoneal metastases, and exhibit 5-year survival rates <30%. A subset of these tumours, defined as "immunoreactive," overexpress mRNA encoding the T-cell-recruiting chemokine CXCL10 (10-kDa interferon gamma-induced protein; C-X-C motif chemokine 10). Tumour-infiltrating CD4(+) CD8(+) T-cells are a well-documented, positive prognostic indicator for HGSOC patients; paradoxically, however, patients diagnosed with HGSOC (overexpressing CXCL10 and therefore theorised to recruit T-cells) typically exhibit poor survival. Recently, an "antagonistic" CXCL10 variant was identified that inhibited leucocyte recruitment to inflamed liver in vivo (Casrouge et al., J Clin Invest 2011;121:308-17). We hypothesised that "immunoreactive" HGSOC might also express antagonistic CXCL10, interfering with leucocyte recruitment and contributing to poor patient prognosis. CXCL10 expression was analysed in HGSOC tissues grouped according to pathology, grade and FIGO stage at diagnosis, and its localisation and association with T-cells established by immunohistochemical staining in tissue microarrays. CXCL10 expression was increased in a subset of serous epithelial tumour samples; however, it did not correlate well with CD45-positive tumour infiltrate. Immunoprecipitation and de novo sequence analysis of CXCL10 identified the N-terminally cleaved, "antagonistic" variant of CXCL10 specifically in malignant tumours, and not in benign ovarian disease. The data demonstrate the presence of the antagonistic form of CXCL10 in HGSOC for the first time, and provide a partial explanation for reduced leucocyte infiltration observed in these tumours. We suggest that CXCL10 cleavage and subsequent antagonism of immune cell recruitment may be a feature of the "immunoreactive" HGSOC subtype, leading to early impairment of the immune response and subsequently worsening patient prognosis.