Endometrial hyperplasia as a risk factor of endometrial cancer

Endometrial hyperplasia (EH) is the precursor lesion for endometrioid adenocarcinoma of the endometrium (EC), which represents the most common malignancy of the female reproductive tract in industrialized countries. The most important risk factor for the development of EH is chronic exposure to unopposed estrogen. Histopathologically, EH can be classified into EH without atypia (benign EH) and atypical EH/endometrial intraepithelial neoplasia (EIN). Clinical management ranges from surveillance or progestin therapy through to hysterectomy, depending on the risk of progression to or concomitant EC and the patient´s desire to preserve fertility. Multiple studies support the efficacy of progestins in treating both benign and atypical EH. This review summarizes the evidence base regarding risk factors and management of EH. Additionally, we performed a systematic literature search of the databases PubMed and Cochrane Controlled Trials register for studies analyzing the efficacy of progestin treatment in women with EH.

PATTERNS OF MYOINVASION IN ENDOMETRIOID ADENOCARCINOMA OF ENDOMETRIUM

Objective: To assess the patterns of myoinvasion of endometrial endometrioid adenocarcinoma, their frequencies in our hospital and to correlate these patterns with survival. Study Design: Retrospective observational study. Place and Duration of Study: Department of Pathology, Shaukat Khanum Memorial Cancer Hospital & Research Centre, Lahore, from Aug 2019 to Apr 2020. Methodology: All cases of endometrial endometrioid adenocarcinoma between 2015 and 2017 were retrieved from the archives, independently reviewed by two researchers, all key reporting parameters recorded in addition to the pattern of myoinvasion as per their operational definitions described by Cole and Quick. The follow-up of 3-5 years was obtained from archives and through telephonic contact for outside hospital patients. Disease free survival and relapse-associated mortality were represented through Kaplan-Meier curves. Results: Eighty cases of myoinvasive endometrial endometrioid adenocarcinoma were reviewed. We found that infiltrating irregular gland pattern was the most frequent in all the age groups. Thirty-five (43.75%) cases showed this type of invasion, followed by broad front pattern 23 (28.75%), Microcystic Elongated and Fragmented (MELF) pattern 15 (18.75%) and adenomyotic pattern 6 (7.5%). One case showed a combination of the last two patterns, whereas adenoma malignum pattern was not seen. Follow-up of these patients showed 8 (10%) patients with relapse related mortality including 5 (62.5%) infiltrating irregular glands, 2 (25%) adenomyosis-like and 1 (12.5%) broad front pattern of myoinvasion. Seventy-two (90%) patients had recurrence free survival. Conclusion: Frequency of infiltrating irregular pattern of myoinvasion in endometrial endometrioid adenocarcinoma is high and associated with recurrence related mortality. Recognition....................

Use of diffusion-weighted imaging and diffusion tensor imaging in assessment of myometrial invasion in patients of endometrial carcinoma and its correlation with histopathological grading (Prospective study)

Background Endometrial cancer (EMC) is considered one of the most common gynecological cancers worldwide. In particular, the depth of myometrial invasion and histological grade of endometrial cancers (EMCs) are strong prognostic factors. Diffusion tensor measurements as mean diffusivity (MD) and fractional anisotropy (FA) values could be useful for assessing the depth of tumor invasion and its histological grade. The study aimed to evaluate the role of diffusion-weighted imaging (DWI) and diffusion tensor imaging in the detection of myometrial invasion in cases of endometrial carcinoma and prediction of its grade in vivo. Results This study included 50 female patients with pathologically proved endometrial carcinoma, and their ages ranged from 38 to 67 years; the mean age was 56.15 years (± 8.229 standard deviation “SD”). There was a significant statistical difference regarding the mean values of diffusion tensor fractional anisotropy (DT-FA), diffusion tensor mean diffusivity (DT-MD) and diffusion-weighted apparent diffusion coefficient(DW-ADC) values in differentiating between intact and infiltrated myometrium with (P value ≤ 0.001). The accuracy of DT-MD, DT-FA and DWI-ADC was 98%, 90% and 86%, respectively, in the detection of myometrial invasion. There was a statistically significant difference in the mean values of DT-FA, DT-MD and DW-ADC for differentiating endometrioid adenocarcinoma grades with the overall P values (˂0.001). The accuracy of DT-FA, DT- MD and DWI-ADC for differentiating grade 3 from grade 1 or 2 endometrioid adenocarcinoma was 94.9%, 84.6% and 74.4%, respectively. For differentiating grade 1 from grade 2 or 3 endometrioid adenocarcinoma, the accuracy of DT-FA, DT-MD and DWI-ADC was 90%, 89.7% and 84.6%, respectively. Mean DT-FA, DT-MD and DW-ADC values were inversely proportional to the degree of pathological grading with r = − 0.867, − 0.762 and − 0.706, respectively. Conclusion Diffusion tensor imaging and DWI are helpful in the assessment of myometrial invasion and have a high negative correlation with histopathological grading in patients with endometrial cancer.

Malignant transformation of endometriosis on vaginal cuff after hysterectomy: a case report

Objective. Endometriotic tissue implants rarely transform to malignant tissue, especially in a patient with a hysterectomy and bilaterally salpingo-oophorectomy. However, several cases with cancer arising from endometriosis after hysterectomy were reported in the literature. Hormone replacement therapy only with estrogen is a crucial risk factor for malignant transformation of persistent endometriotic tissue. Case Report. The present case demonstrates an endometrioid adenocarcinoma arising from persistent endometriosis tissue in a patient who was performed hysterectomy with bilateral salpingectomy 3 years ago. The histopathologic specimens of the previous surgery did not include any malignant tissue. After 3 years, she applied to the hospital with abnormal vaginal bleeding, and her histopathologic examination result found an ulcerated mass at the upper one-third of the vagina that is compatible with endometrioid adenocarcinoma. Conclusion. It is crucial to keep in mind the endometriosis history of the patient, to be able to diagnose cancer arising from endometriosis while evaluating the patient with a hysterectomy.

ASSOCIATION OF STEROID RECEPTOR EXPRESSION WITH THE CLINICAL AND HISTOLOGICAL FINDINGS IN PATIENTS WITH ENDOMETRIAL CANCER

Objective: To determine the association of estrogen and progesterone receptor expression with the clinical and histological findings of endometrial cancer. Study Design: Prospective observational study. Place and Duration of Study: Jinnah Postgraduate Medical Centre, Karachi between Sep 2017 to Oct 2019. Methodology: A total of 130 patients were diagnosed with endometrial carcinoma. Data from patient files were collected regarding tumour histology, grade, stage, tumour receptor expression, and the clinical characteristics: parity, menopausal status. The receptor expression profile was documented for each patient. Data were analyzed using SPSS version 25. The association between ER/PR expression categories and clinical/histological features were explored using the chi-square test. Results: The estrogen and progesterone receptor expressions were significantly associated with low-grade (Grade I and II) tumours and with Stage I and Stage II endometrial carcinoma with p<0.001. About 34 (34.7%) cases of endometrioid histology were negative for both estrogen and progesterone receptors. The ER and PR negativity was strongly associated with Grade III endometrial cancer (p=0.003). The majority of the stage IV cancers were negative for both the ER and PR receptors with a p<0.001. Conclusion: Estrogen and progesterone positivity was associated with endometrioid adenocarcinoma, well-differentiated, and less advanced stage of endometrial cancer at the time of diagnosis.

Expression of Cell Adhesion Molecules in Endometrial Tissue and Endometrioid Adenocarcinomas

Endometrioid endometrial adenocarcinomas are the most common histological variant of malignant tumors in the uterine cavity. In turn, the features of expression by neoplastic cells of intercellular adhesion molecules are a reliable prognostic factor in the progression of malignant tumors. One of the important indicators of cancer progression is E-cadherin, which determines the strength of intercellular adhesion and the ability of cells to spread. Among other adhesion molecules, considerable attention has recently been paid to the molecules of cell adhesion of carcino-embryonic antigen 1 (MCA-REA1). Therefore, the purpose of the study was to study the expression of E-cadherin and MCA-REA1 in normal endometrium and endometrioid adenocarcinomas. Materials and methods. To achieve this purpose, we performed tissue studies of 10 samples of normal endometrium and 30 samples of endometrioid endometrial adenocarcinoma (8380/3). Morphological features of neoplastic tissue were studied by hematoxylin and eosin staining. Visualization of E-cadherin and MCA-REA1 receptors was determined using the appropriate antibodies and the UltraVision Quanto Detection System HRP DAB Chromogen (Thermo scientific, USA) in similar areas of the tumor on serial sections. Results and discussion. It has been shown that endometrial tissue demonstrates different expression of MCA-REA1 and E-cadherin receptors in the normal state and in endometrioid adenocarcinomas. This indicates the absence of any functional correlation between them. Expression of MCA-REA1 was detected on the apical surface of the luminal and glandular columnar epithelium. In contrast, the endometrioid endometrial carcinoma tissues showed the pronounced heterogeneous location of MCA-REA1 in tumor cells. Moreover, due to the tumor dedifferentiation, these proteins disappear from the cell surface. On the other hand, E-cadherin is normally localized in intercellular contacts and epithelial-mesenchymal junctions. During carcinoma dedifferentiation, the intensity of E-cadherin expression decreased, which was accompanied by an increase in nuclear polymorphism of cancer cells and focal separation of cells from the total tumor mass. Conclusion. The variability of the expression patterns of MCA-REA1 and E-cadherin in the dedifferentiation of endometrioid adenocarcinoma may be an indicator of neoplastic transformation and progression of the malignant process

Knockdown of LMTK3 in the Endometrioid Adenocarcinoma Cell Line Ishikawa: Inhibition of Growth and Estrogen Receptor α

ObjectiveThe curative effect of high-efficiency progesterone and other therapeutic drugs for endometrioid adenocarcinoma patients with preservation of reproductive capacity has not been satisfactory so far. Novel therapeutic drugs need to be explored.MethodsWe investigated the cytoplastic and nuclear expression levels of LMTK3 between endometrioid adenocarcinoma tissues and adjacent endometrial tissues by immunohistochemistry. We detected the effects of LMTK3 on cell viability of Ishikawa cells by CCK-8. We detected the effects of LMTK3 on cell cycle and apoptosis of Ishikawa cells by flow cytometry. We also detected the effects of LMTK3 knockdown on mRNA and protein levels of ERα by qRT-PCR and western blotting, respectively. We also used the cBioPortal online database to analyze the coexpression of LMTK3 and ESR1 in 1647 UCEC samples.ResultsWe used TMAs to identify that LMTK3 was mainly detected in the cytoplasm of endometrioid tissues, and cytoplasmic LMTK3 expression in endometrioid tissues was higher than that in adjacent endometrial tissues (P &lt; 0.05). LMTK3 knockdown decreased the proliferation of Ishikawa cells through decreasing cell viability (P &lt; 0.01), increasing G1 (P &lt; 0.001) arrest, and promoting apoptosis (P &lt; 0.01). There was a positive correlation between the mRNA expression levels of LMTK3 and ESR1 (Spearman: P=2.011e-5, R=0.13; Pearson: P=7.18e-8, R=0.17). Knockdown of LMTK3 also reduced the mRNA (P &lt; 0.001) and protein (P &lt; 0.001) levels of ERα.ConclusionsInhibitors of LMTK3 may be a possible future treatment for ERα and LMTK3 highly expressed endometrioid adenocarcinoma following appropriate studies.

EP.TH.717Triple tumour: A myriad of serial incidental findings in a patient presenting with Gallstone pancreatitis

Aim To present a rare incidental synchronous triple tumours - colonic adenocarcinoma, endometroid ovarian adenocarcinoma and benign Brenner tumour in a patient admitted with acute gallstone pancreatitis. Methods A 75-year-old female presented with epigastric pain. Blood-tests and USS abdomen confirmed gallstones and pancreatitis. She was treated conservatively. USS also showed incidental pelvic mass which was further characterised by CT and MR scans. These scans confirmed heterogeneous lobulated mass in the left adnexa. CT scan also picked-up incidental mass in transverse colon, which was confirmed as cancer by colonoscopy. She was offered therapeutic resection after discussion in Colorectal and Gynaecology MDT. Intra-operatively, transverse colonic tumour was invading into the proximal ileum. Laprascopic surgery concluded with extended right hemicolectomy, small bowel resection-anastomosis, omentectomy, total abdominal hysterectomy and bilateral salpingo-oophorectomy. Results The patient had gradual recovery without any complications. Histopathology showed T4N2 poorly differentiated adenocarcinoma of colonic mass, FIGO grade 1 stage 1c endometrioid adenocarcinoma of left ovary and benign brenner tumour of right ovary. Post-operative MDT did not offer adjuvant-therapy due to slow recovery and fraility. So far, two-years of follow-up did not show any recurrence. Conclusion This report adds to the limited literature of triple synchronous tumours, including rare Brenner accounting for 5% of benign ovarian tumours and endometrioid ovarian tumour with an incidence of 4 -7%. Multi-disciplinary approach and combined surgery can achieve a desirable outcome in such complex cases. It is crucial to identify the primary status of the tumours as it will guide the adjuvant treatment.