The forgotten woman's cancer: vulvar squamous cell carcinoma (VSCC) and a targeted approach to therapy.
Growth factors are polypeptides involved in the regulation of normal and malignant cell growth. Transforming growth factor alpha (TGF alpha) is one of such protein growth factors that plays an important role in the regulation of mammalian cell growth. In this study, the expression of TGF alpha mRNA was studied in tissue specimens obtained at the time of surgery from patients with benign and malignant gynecologic proliferative conditions. To analyze TGF alpha mRNA expression we utilized the highly sensitive technique denoted Message Amplification Phenotyping which can detect mRNA in single cells. This technique consists of isolating RNA, reverse transcription of total cellular RNA to produce copy DNA, followed by enzymatic amplification of TGF alpha cDNA fragments using specific TGF alpha primers and polymerase chain reaction. The results showed significant levels to TGF alpha mRNA expression in vulvar (100% of the cases positive), cervical (66% positive), and endometrial (66% positive) carcinomas. Moreover, vulvar condylomas produced by human papilloma virus (HPV) showed the highest levels of TGF alpha mRNA expression of all the pathological tissues examined. In contrast, vulvar melanoma, fibrocystic disease of the breast, and certain ovarian tumors showed undetectable TGF alpha mRNA expression. Normal mesodermal tissues such as myometrium, abdominal rectus muscle, and fallopian tubes were negative for TGF alpha mRNA expression. However, TGF alpha mRNA was present in normal cervix and in normal endometrium. The results showed that TGF alpha mRNA expression is frequently associated with various malignant tumors and HPV-induced lesions of epithelial origin, suggesting that TGF alpha mRNA protein product may be a contributory factor in the progression of these pathological tissue alterations. Finally, TGF alpha mRNA expression was not restricted to malignant cells, suggesting that the TGF alpha mRNA protein product may function as a mitogen in the normal human epithelial tissues examined.