An obese diabetic woman presents with menorrhagia. Curette from endometrium demonstrates endometrial carcinoma. Most probable gene associated with this carcinoma? (Repeat)
Ans: (a) PTEN geneRef: style="font-family: Times New Roman, Times, serif"> of endometrial carcinomaThe 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 carcinomasA beta-catenin mutation was detected in about 20% of endometrioid carcinomasLynch 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 kinaseKRAS, a GTPase that functions in signal transductionCTNNB1, involved in adhesion and cell signaling. The CTNNB1 (beta-catenin) gene is most commonly mutated in the squamous subtype of endometrioid adenocarcinomaPROGNOSTIC VARIABLES IN ENDOMETRIAL CAAge:Younger women with endometrial cancer have better prognosis than older women.Histologic Type:Non-endometrioid histologic subtypes account for about 10% of endometrial cancers and carry an increased risk for recurrence and spreadHistologic gradeTumour size:Significant prognostic factor for lymph node metastasis and survival in patients with endometrial CAHormone receptor status:Estrogen and progesterone receptor levels are prognostic indicatorsPatients 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 invasionIsthmus and cervix extension:Involvement of ishmus and cervix is associated with increased risk for extrauterine disease, lymph node metastasis and recurrencePeritoneal 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 uterusLymph node metastasesIntraperitoneal metastasesMolecular 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.
PTEN
TP53
CDH4
C-myc
Carcinoma Endometrium