Allelic deletion on chromosome 17p13.3 in early ovarian cancer.

Multiple chromosome 17 loci may be involved in ovarian carcinogenesis. Fifty-seven sporadic ovarian epithelial tumors were examined for loss of heterozygosity at 15 loci on chromosomes 17p. Eighty % (39 of 49) of informative tumors had allelic loss in 17p13.3 at D17S30, D17S28, or both loci within this region, including 3 of 7 tumors of low malignant potential and 4 of 5 nonmetastatic carcinomas. The smallest region of overlapping deletions extends from D17S28 to D17S30, a distance of 15 kb. Furthermore, several tumors have breakpoints within the region detected by the D17S30 probe. Chromosome 17p13.3 genes with potential tumor suppressor function include HIC-1, DPH2L (N. J. Phillips et al. Isolation of a human diphthamide biosynthesis gene on chromosome 17p13.3, submitted for publication)/OVCA1, PEDF, and CRK. The HIC-1 coding sequence lies i kb centromeric to the D17S28-S17S30 region of deletion (M. Makos Wales et al., Nat. Med., 1:570-577, 1995) but remains a candidate because 5'-regulatory elements may lie within the critical region. Portions of the DPH2L/OVCA1 coding sequence lie within the D17S28-D17S30 interval. Somatic cell hybrid analysis places PEDF in an interval including D17S28, D17S30, and D17S54, whereas CRK is excluded from this interval. Chromosome 17p13.3 loss precedes TP53 and BRCA1 region deletions because the latter changes are see only in high-stage carcinomas. Microsatellite instability plays only a minor role in sporadic ovarian carcinogenesis because only 1 of 57 tumors showed this finding.

Expression of metallopanstimulin in condylomata acuminata of the female anogenital region induced by papilloma virus.

We have identified by cDNA cloning a gene, denoted MPS-1, that is activated in cultured human transformed cells by growth factors. The MPS-1 gene contains one zinc finger domain similar to those present in the C4 family of DNA binding proteins. In this study, the expression of MPS-1 mRNA and protein were examined in HPV-induced human condylomata acuminata. Initially, we detected the presence of MPS-1 mRNA by message amplification phenotyping in all condylomata tissues examined. Subsequently, the cellular distribution and abundance of MPS-1 mRNA was studied by in situ hybridization with specific MPS-1 DNA and RNA probes. We found that MPS-1 mRNA is expressed at high levels in the cytoplasm of condylomata cells. In contrast, the MPS-1 mRNA is expressed at low levels in nonneoplastic tissues. Moreover, antibodies were raised against the predicted N-terminal sequence of the MPS-1 protein and used to detect MPS-1 in condylomata cells. MPS-1 immunoreactivity was detected in the cytoplasm and/or the perinuclear regions of condylomata cells, with marked staining in areas of active proliferation. In distinction, MPS-1 immunoreactivity was very weak in normal epithelial cells. The results support the contention that the MPS-1 protein may be a potentially important mediator of proliferative responses induced by HPV.

Expression of transforming growth factor alpha mRNA in benign and malignant tissues derived from gynecologic patients with various proliferative conditions.

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.

Tratamiento primario del carcinoma de mama, factores pronosticos. / Primary treatment of breast carcinoma. Prognostic factors

155 pacientes con un seguimiento minimo de 3 anos fueron evaluados. La demora en la consulta no influyo en la incidencia de ganglios metastasicos. El 73.5% de las parecurrencia o metastasis a los 3 y 5 anos T3, T4). El 56% presento metastasis en los ganglios axilares. El tamano tumoral influyo en la incidencia de metastasis axilares excepto cuando se comparo T1 con T2 (PO. 06). Cuando se correlaciono tamano tumoral (T) con el estado de ganglios y recurrencia o metastasis a los 3 y5 anos no se observo diferencia significativa.Los pacientes con ganglios positivos tuvieron peor pronostico que las con ganglios negativos a los 3 y 5 anos (P 0.01). El estado menopausico no influyo en la sobrevida libre de enfermedad. El 87% de las pacientes con recurrencia a los 5 anos presentaron enfermedad diseminada. Los resultados terapeuticos a los 5 anos son similares a los publicados por otros autores en U.S.A.y Europa

Tratamiento primario del carcinoma de mama, factores pronosticos. / Primary treatment of breast carcinoma. Prognostic factors

155 pacientes con un seguimiento minimo de 3 anos fueron evaluados. La demora en la consulta no influyo en la incidencia de ganglios metastasicos. El 73.5% de las parecurrencia o metastasis a los 3 y 5 anos T3, T4). El 56% presento metastasis en los ganglios axilares. El tamano tumoral influyo en la incidencia de metastasis axilares excepto cuando se comparo T1 con T2 (PO. 06). Cuando se correlaciono tamano tumoral (T) con el estado de ganglios y recurrencia o metastasis a los 3 y5 anos no se observo diferencia significativa.Los pacientes con ganglios positivos tuvieron peor pronostico que las con ganglios negativos a los 3 y 5 anos (P 0.01). El estado menopausico no influyo en la sobrevida libre de enfermedad. El 87% de las pacientes con recurrencia a los 5 anos presentaron enfermedad diseminada. Los resultados terapeuticos a los 5 anos son similares a los publicados por otros autores en U.S.A.y Europa

Adriamycin alone or in combination in 100 patients with carcinoma of the cervix or vagina.

One hundred consecutive evaluable patients with advanced carcinoma of the cervix or vagina were treated with doxorubicin (Adriamycin) alone or in combination. The use of Adriamycin in conjunction with cyclophosphamide and 5-fluorouracil resulted in the highest response rate with all responders continuing to respond.

Pelvic lymphadenectomy in women with carcinoma of the clitoris.

Thirty-three women with carcinoma of the clitoris underwent surgical therapy, and 12% subsequently developed pelvic recurrence. However, none of the 18 patients without initial evidence of inguinal node metastases developed a pelvic recurrence. Of the 15 women with initial evidence of inguinal node metastases, 26.6% developed pelvic recurrence. It is, therefore, concluded that the addition of the routine use of pelvic lymphadenectomy to radical vulvectomy and bilateral inguinal lymphadenectomy in women with carcinoma of the clitoris is not warranted and that only those patients with histologically proven inguinal node metastases should undergo pelvic lymphadenectomy. If pelvic node metastases are documented, it is suggested that such patients receive postoperative pelvic irradiation.