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.

Investigating the Factors Associated with the Level of Expression of Estrogen and Progesterone Receptors in Patients Suffering from Colorectal Cancer

Background. The present study was performed to investigate the factors related to the expression level of estrogen and progesterone receptor in patients with colorectal cancer. Material and Methods. This crosssectional study was performed on 54 patients suffering from colorectal cancer referring to Imam Reza Hospital in Birjand during 2018-2019. After the biopsy performed during surgery, the specimen was sent for immunohistochemistry, and the status of receptors was determined. Eventually, the data were analyzed by SPSS 22. Results. Out of the 54 patients studied, 64.8% were male. The mean age of the patients was 62.28 ± 14.03 years. The level of expression of beta-estrogen receptors and progesterone receptors had a significant relationship with age, consuming drugs of abuse, and familial history ( P = 0.001 ). Also, the level of expression of estrogen and progesterone receptors of patients with a more advanced stage of cancer was significantly lower ( P = 0.001 ). Conclusion. The extent of expression of estrogen and progesterone receptors affects the progression and prognosis of disease. Thus, through hormone therapy, a step can be taken to reduce the progression and even to treat colorectal cancer.

An unusual nicotinamide derivative, 4-pyridone-3-carboxamide ribonucleoside (4PYR), is a novel endothelial toxin and oncometabolite

Our recent studies identified a novel pathway of nicotinamide metabolism that involves 4-pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR) and demonstrated its endothelial cytotoxic effect. This study tested the effects of 4PYR and its metabolites in experimental models of breast cancer. Mice were divided into groups: 4T1 (injected with mammary 4T1 cancer cells), 4T1 + 4PYR (4PYR-treated 4T1 mice), and control, maintained for 2 or 21 days. Lung metastasis and endothelial function were analyzed together with blood nucleotides (including 4PYR), plasma amino acids, nicotinamide metabolites, and vascular ectoenzymes of nucleotide catabolism. 4PYR metabolism was also evaluated in cultured 4T1, MDA-MB-231, MCF-7, and T47D cells. An increase in blood 4PYR in 4T1 mice was observed at 2 days. 4PYR and its metabolites were noticed after 21 days in 4T1 only. Higher blood 4PYR was linked with more lung metastases in 4T1 + 4PYR vs. 4T1. Decreased L-arginine, higher asymmetric dimethyl-L-arginine, and higher vascular ecto-adenosine deaminase were observed in 4T1 + 4PYR vs. 4T1 and control. Vascular relaxation caused by flow-dependent endothelial activation in 4PYR-treated mice was significantly lower than in control. The permeability of 4PYR-treated endothelial cells was increased. Decreased nicotinamide but enhanced nicotinamide metabolites were noticed in 4T1 vs. control. Reduced N-methylnicotinamide and a further increase in Met2PY were observed in 4T1 + 4PYR vs. 4T1 and control. In cultured breast cancer cells, estrogen and progesterone receptor antagonists inhibited the production of 4PYR metabolites. 4PYR formation is accelerated in cancer and induces metabolic disturbances that may affect cancer progression and, especially, metastasis, probably through impaired endothelial homeostasis. 4PYR may be considered a new oncometabolite.

147 Association of Estrogen Receptor and Porgesteron Receptor Positivity with Nodal Involvement, Menopause Status and Stage of Primary Invasive Carcinoma of Breast Among Patients Presenting to Fauji Foundation Hospital, Islamabad

Aim To determine the percentage of estrogen and progesterone receptor positivity along with histological variants, stage, and menopausal status among carcinoma breast patients in our setup. Method This was a retrospective observational study. Data from records of patients with breast carcinoma presenting at Oncology Department Fauji Foundation Hospital, Islamabad was evaluated. H+E stained slides from 431 cases with carcinoma breast, patients over the age of 18 years, were reviewed and the presence of invasive carcinoma was confirmed in all cases. Patients with metastases were excluded. Paraffin blocks were assessed immunohistochemically for estrogen and progesterone receptor expression. Histological subtypes, stages of tumors, and nodal involvement were also noted. Data were analyzed using SPSS. Results Records of 431 patients were evaluated. The median age was 53 years. The most common histological variant was invasive ductal carcinoma. 4.6% of patients had stage I, 33.4% had stage II, 40% had Stage III and 22% had Stage IV disease. Overall, 62% had node-positive disease. Overall ER+, PR+, ER+/PR+, ER+/PR-, ER-/PR+ and ER-/PR- percentages were 52%, 54%, 42%, 11%, 12% and 35% respectively. 38% of patients were premenopausal, 59% were postmenopausal and 3% were perimenopausal. Patients with node positive diseases were 51% ER+,55% PR+, 43% ER+/PR+, 8% ER+/PR-, 12% ER-/PR+ and 37% ER-/PR-. Conclusions The percentage of ER/PR+ is the highest in our study. Pre-menopausal patients showed approximately equal positivity to post-menopausal patients. Node positive enrolments had increased positivity of ER/PR receptor.

Estrogen and Progesterone Receptor Immunoexpression in Fallopian Tubes among Postmenopausal Women Based on Time since the Last Menstrual Period

Existing data on the expression of estrogen receptor (ERα) and progesterone receptor (PR) in fallopian tubes in postmenopausal women are mostly inconclusive. Therefore, we assessed ERα and PR immunoexpression in the oviducts of these women. One hundred postmenopausal women were divided into three groups based on time elapsed since the last menstrual period: (A) 1–5 years, (B) 6–10 years, and (C) ≥11 years. In all groups, both in the glandular epithelium and stroma of the ampulla and isthmus of the oviduct, immunolocalization of ERα and PR were noted. The glandular epithelium of the ampulla showed a higher percentage of PR-positive cells than the isthmus in each group. Regarding ERα, there were no significant differences. In the glandular epithelium in both the ampulla and isthmus, the percentage of ERα- and PR-positive cells was significantly higher than that in the stroma in each study group and higher in the A group than in the C group. In conclusion, in postmenopausal women, time elapsed since the last menstrual period in the fallopian tubes was positively correlated with the following: (1) the epithelium showed vacuolation of cytoplasm with greater frequency, (2) the proportion of ciliated cells decreased, and (3) the percentage of ERα- and PR-positive cells also decreased. The obtained results indicate a significant decrease in ERα and PR expression depending on the time that has elapsed since the last menstruation, which is undoubtedly related to the loss of the reproductive function of the patients.

Markers of Aggressiveness in Craniopharyngiomas

Craniopharyngiomas (CP) are rare tumors that may be locally aggressive. The presence of functional estrogen receptors (ER) has been reported in CP and might be related to risk of recurrence. Our aim is to ascertain if the expression estrogen and progesterone receptor (PR) might be associated with to recurrence in CP. Material and Methods: Descriptive retrospective observational study of patients with confirmed histology of CP and tissue sample available admitted to Virgen Del Rocio University Hospital (Seville, Spain) from January 1967 to October 2020 were included. Estrogen and progesterone receptor expression was analyzed by Immunohistochemistry. Ki-67 levels were also analyzed. Two CP groups were considereded according to Ki67 levels: Group A (Ki67&lt;10%) and group B (Ki67&gt;10%). As all variables followed a non-parametric distribution, U Mann Whitney, Chi-Square, and Z-test with Benjamini-Hochberg correction were used when needed. Results: Our study population includes 80 patients (46 male and 34 female), with a median age at diagnosis of 34 years [10-50.00]. Twenty-six patients were under 18 years old (children) with a median age of 7 years [4.5-10.00], and 54 were adults (aged 18 and above) with a median age of 45 years [33-58.50]. Our data shows higher recurrence rates when Ki67 levels staining were higher than 10%: 8/14 (57.2%) in comparison with Ki67&lt;10% (6/14, 42.9%, p=0.018). In children we found 6 samples with Ki67&lt;10% and 6 samples with Ki67 &gt;10%; recurrences were observed in 2/6 (33,3%) in the first group and in 6/6 (100%) in the second, respectively (p= 0,199). In adults, we found 9 and 3 patients for high and low Ki67 levels, respectively. Recurrences were observed in 4/9 (44,4%) in the group A and in 2/3 (66,7%) in the group B, respectively (p= 0,28). There were no differences between age groups. In patients with positive ER, we observed an increased rate of recurrence: 12/23 (52.17%) versus 2/13 (15,38%) in patients with negative ER stain but it was no significant. (p=0,21). No association between PR and recurrence was observed. Conclusions: In our series, patients with CP with high Ki67 levels are more likely to recur. No clear association between ER, PR expression and recurrence was observed. These findings support the use of Ki67 as a marker of recurrence in CP. Sources of Research Support: Spanish Ministry of Health, ISCIII co-funded with Fondos FEDER (PI16/00175) and Novartis Oncology Spain.