Role of TGF-beta signaling and Ski/SnoN mRNA expression in cervical carcinomas / 대한산부인과학회잡지

OBJECTIVE: TGF-beta signaling is dependent on the heterodimerization of the type II TGF-beta receptor (TbetaR-II) with the type I TGF-beta receptor (TbetaR-I). which mediate intracellular signals through Smad proteins. Whereas physiologic concentrations of SnoN and Ski allow a feedback regulation of TGF-beta signaling, deregulation of SnoN or Ski expression leads to total inhibition of TGF-beta signaling and of the tumor suppressors Smad2 and Smad4, which can explain the role of SnoN and Ski as oncogenes. In order to identify possible molecular mechanisms responsible for TGF-beta resistance, the author investigated the mutation and expression of TGF-beta1, its receptors, Ski/SnoN in cervical carcinomas. METHODS: From December 1995 to December 1999, 45 carcinomas and 7 normal cervical tissue specimens were obtained by surgical resection in the Kyung Hee University Medical Center. Tissue specimens were snap-forzen in liquid N2 and stored at -70 degrees C until used. Total RNA was extracted from specimens and evaluated the expression levels using densitometric analysis of quantitative RT-PCR products (TGF-beta1, Tbeta1R-I, Tbeta1R-II, Ski/SnoN), and the mutations were investigated by quantitative genomic-PCR followed by nonisotopic RT-PCR-SSCP analysis (Tbeta1R-II, Tbeta1R-I, Ski/SnoN). The abnorally expressed levels of RT-PCR products (TGF-beta1, Tbeta1R-II) were analysed for the clinicopathologic characteristics. RESULTS: Quantitative RT-PCR analysis demonstrated variable expression of TGF-beta1 mRNA (0.05-0.89) in tumors and significantly increased TGF-beta1 expression level (>0.48) in 15 of 45 samples (33.3%). There is no significant reduction of Tbeta1R-I expression (1.36) in 2 of 45 samples (4.4%), and there is no amplification of Ski/SnoN gene by quantitative genomic-PCR analysis. CONCLUSIONS: The overexpression of TGF-beta1 mRNA and the reduced or absent expression of Tbeta1R-II may be an important contributing factors, and the abnormally low genomic levels and no mutational alterations of Tbeta1R-II is caused by monoallelic deletion suggesting that Tbeta1R-II might play as a tumor suppressor of haloinsufficiency in cervical carcinomas. We could not show that high levels of Ski/SnoN expression could produce a disruption of TGF-beta signaling in cervical carcinomas.

A Case of Primary Malignant Melanoma of the Vagina: Vulvovaginal Reconstruction Using Gracilis My ocutaneous Flap Afer Radical Surgery / 대한부인종양콜포스코피학회잡지

Primary malignant melanornn of the vagina is rare, with only about 130 reported cases worldwide. They presumably arise from melanocytes that are present in the vagina in 3% of normal wornen. Vaginal melanoma accounts for less than 1% of melanomas and less than 3% of primary malignant tumors of the vagina. Most of patients complain vaginal bleeding, vaginal discharge, foreign body sensation in order. The best treatment of vaginal melanoma rernains eni.gmatic, Many authors indicate that radical surgery may be the pcferred approach and the number of reported cases treated with radical surgery is increasing. But other author comment that no significant change in survival is apparent with radical surgery. Overall prognosis is poor as most patients have deeply penetrating lesions at the time of diagnosis. Recently, not only the effort to increase the survival rate but the quality of life including sexual function after treatment is becoming an important issue about treatment ot cancer patients. We experienced a case of primary malignant melanoma of the vagina treated with radical surgery and restored the sexual function by vulvovaginal reconstruction using gracilis myocutaneous flap. So we report this case with brief literature review.