An obese woman with type 2 diabetes and hypertension is diagnosed with endometriod type of endometrial carcinoma. Most probable gene defect expected in this condition is:
PTEN
p53
MSH2
BRCA2
A i.e. PTEN geneRef: style="font-size: 1.04761904761905em; font-family: Times New Roman, Times, serif"> of endometrial carcinomaExplanation:The most frequently altered gene in estrogen-dependent endometrioid endometrial carcinoma is PTEN.In contrast, p53 mutations or Her2/neu overexpression are more frequent in non-endometrioid tumors.K-ras mutations are detected in approximately 15-30% of endometrioid carcinomas.A beta-catenin mutation was detected in about 20% of endometrioid carcinomas.Lynch syndrome, which is an autosomal dominant inherited disorder of cancer susceptibility and is characterized by a MSH2/MSH6 protein complex deficiency, is associated with the development of non- endometrioid carcinomas.Also Know:The genetic mutations most commonly associated with endometrioid adenocarcinoma are in the genes:PTEN, a tumor suppressor gene*.PIK3CA, a kinase.KRAS, a GTPase that functions in signal transduction.CTNNB1, involved in adhesion and cell signaling. The CTNNB1 (beta-catenin) gene is most commonly mutated in the squamous subtype of endometrioid adenocarcinoma.PROGNOSTIC VARIABLES IN ENDOMETRIAL CAAge:Younger women with endometrial cancer have better prognosis than older women.Histologic Type:Nonendometrioid histologic subtypes account for about 10% of endometrial cancers and carry an increased risk for recurrence and spread.Histologic grade.Tumour size:Significant prognostic factor for lymph node metastasis and survival in patients with endometrial CA.Hormone receptor status:Estrogen and progesterone receptor levels are prognostic indicators,Patients whose tumours are positive for one or both receptors have longer survival times,Progesterone receptors levels appear to be stronger predictors of survival.DNA ploidy and proliferative Index:The proportion of nondiploid tumours increases with stage, lack of tumour differentiation, and depth of myometrial invasion.Myometrial invasion:Increasing depth of invasion is associated with increasing likelihood of extrauterine spread and recurrence.Lymph-vascular space invasion.Isthmus and cervix extension:Involvement of isthmus and cervix is associated with increased risk for extrauterine disease, lymph node metastasis and recurrence.Peritoneal cytology:Seems to have adverse effect on survival only if the endometrial cancer has spread to adnexa, peritoneum, or lymph nodes and not if the disease is otherwise confined to uterus.Lymph node metastases.Intraperitoneal metastases.Molecular aberration.Inactivation of PTEN tumor suppressor gene is one of the earliest aberrations observed and most common genetic defect in Type 1 cancer.Most frequent genetic alteration is TP53 mutation found in Type 2 endometrial cancer.
Gynaecological Disorders in Obs.