![]() Minimal deviation ADC (adenoma malignum: MDA) and its related endocervical tumors such as lobular glandular endocervical hyperplasia (LEGH),atypical LEGH,and ADC in situ including endocervical dysplasia had been classified in 2014 WHO classification. Only frank invasive ADC serves easily the specimen diagnosed malignant. From this issue,even if blush-taken cytology,or endocervical curettage,it is very difficult to diagnose AIS,or micro invasive ADC. The macroscopic observation is often impossible even if endoscopy. If the foci located near squamous-columnar junction (SCJ),it is easy to biopsy,but most of the cases the abnormal lesion located deep in glands along with narrow cervical canal. The issue of diagnosis depends on the location of foci. WHO 2014 classification has involved GAS as new subtype of ADC which had SKT11 mutation (WHO 2014) ( 12).Īs for cytology,the expression of atypical glandular cells (AGC) by PAP smear test such as AGC is unstable and the subsequent re-examination or endocervical curettage reveals often negative,and further precise absolute examination must be excisional conization or hysterectomy. Activation of AMPK-related kinases by LKB1 plays vital roles maintaining cell polarity thereby inhibiting inappropriate expansion of tumor cells. Activation of AMPK by SKT11 suppresses tumor growth and proliferation when energy and nutrient levels are scarce. STK11 (LKB1) is a member of serine/threonine kinase family and regulates cell polarity and suppresses tumor genesis via adenine monophosphate-activated protein kinase (AMPK) which is member of PI3K-mTOR pathway. Patients with PJS have a cancer risk in cervix,such as lobular endocervical glandular hyperplasia (LEGH),or minimal deviation adenocarcinoma (MDA) and mutinous ADC,which depends on STK11 mutation ( 11). Germ line mutations in this gene have been associated with Peutz-Jeghers syndrome (PJS). There might unknown heterogeneity of EGFRs’ dimerizations.Īmong them,STK11 was suspected as a responsible gene mutation of GAS. reported no case of EGFR mutation in their data set. Patients with the ADC subtype of cervical cancer may benefit from targeted agents known as MEK inhibitors,which have shown some success in clinical trials ( 9). They found that 31 percent of the samples had PIK3CA mutations 17.5 percent of the ADC (and non-SCC) had KRAS mutations and 7.5 percent of the SCC (but none of the ADC) had a rare mutation in the gene EGFR. ( 10) reported the comparison of the spectrum of cancer-related gene mutations in the two main subtypes of cervical cancer ADC and SCC. On the other hand,Harvard group,Wright et al. ![]() GAS,which driver gene has not been elucidated,had somatic gene mutations such as ERBB2 (Her2/neu2),k-Ras,PIK3CA,STKⅡ,ELF3,and CBFB ( 8). In speculation,HPV 18 and 16 and their proteomes thought to be responsible for oncogenesis with estrogens which stimulate the endometrioid type’s and endocervical type’s proliferation,but recently new entity of gastric type adenocarcinoma (GAS) was detected and its prognosis is worst among subtypes of ADC ( 9). The oncogenesis of ADC has not been elucidated in precise. This article focuses on up-to-date knowledge of biology and possible specific therapeutic directions to explore in the management of cervical ADC. Bevacizumab (Bev, anti-VEGF monoclonal antibody) is considered as one of key agent with paclitaxel and carboplatin in SCC, but not for ADC. The targets of oncogenic driver mutations were vascular endothelial growth factor (VEGF) in SCC, or tyrosine kinase (TK) of endothelial growth factor receptor 2 (EGFR2, Her2/neu)-Ras-MAPK-ERK pathway. Further molecular targeted therapy (MTT) has been studied. As for chemotherapy (CT), the induction CT has not established, as well. The worse biological behavior had been reported in patients with intermediate- and high risk factors after surgery, and in advanced stage over Ⅲ, radiotherapy (RT) alone and concurrent chemo-radiotherapy (CCRT) with cisplatin was not always effective. It comprises nearly 20-25% of the all cervical malignancy in developed countries. Uterine cervical adenocarcinoma (ADC) has been increasing in its prevalence world widely despite the decrease of squamous cell carcinoma (SCC).
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