Primary fallopian tube cancer

• Primary fallopian tube cancer (PFTC) is a rare and aggressive gynecologic malignancy and it accounts for less than 5% of all genital female cancers according to the Swedish Cancer Registry. In a retrospective study we have analysed histopathological, clinical, biological and prognostic factors among patients with PFTC. 128 cases of PFTC treated between 1923 and 1991 were histopathologically reviewed and retrospectively staged according to the new FIGO staging system. Seventy-four percent were found to be instage Ia-IIa, compared to 36% in stage Ia-IIa among ovarian cancer cases treated at Radiumhemmet in 1958 to 1973. In stage Ia a 5-year actuarial survival of 70.1% was demonstrated. Forty-five percent were nulliparous and the mean age at diagnosis was 56 years. Twenty-two per cent were suffering from salpingitis and the infertility rate was 25%. Among the 14 variables studied in the clinical and pathological review and tested in the multivariate analysis the first in rank were the stage (p=0.001) and grade of differentiation of the tumors (p=0.070). Treatment modalities changed during the studied period. Thirty-three per cent of patients underwent surgery with total abdominal hysterectomy and bilateral salpingo oophorectomy. Patients receiving chemotherapy had superior survival rates (p=0.0006) and patients with cisplatinum-containing chemotherapy did better than those without. In this thesis, attempts have been made to further characterize the malignancy potential of the PFTC by biological prognostic factors. The patients in the maternal were divided into two groups according to survival time and the interval was chosen in order to get a maximal contrast with regard to survival at a minimal cost - short-time survivors < 2years and long-time survivors > 8 years. We have evaluated the DNA ploidy content, proliferative activity (MIB-I), p53 overexpression combined or not with the downstream product p21/WAF-I, and tumor angiogenesis (F8) in correlation to clinical outcome. Furthermore, we studied the frequences of p53 mutations in PFTC and in their corresponding metastases/recurrences as well as the influence of p53 on therapeutic effect and clinical course in individual cases with careful clinical follow-up. All PFTCs showed aneuploid DNA distribution patterns. The following investigated biological markers (DNA, MIB-I, P53, p21/WAF-I, F8) could not discriminate between short- and long-time survivors. A tendency to increased frequency of mutations (combined p53 and p21/WAF-I) was found among short-time survivors in stage I as well as in stage IV. Increasing MIB-I correlated to poor survival in a multivariate analysis of stage I cases. MMMT showed aneuploid DNA content patterns. MIB-I, p53, WAF-I, and F8did not allow discrimination between short- and long-time survivors. A comparison of SSCP and CDGE suggests that CDGE is superior as a TP53 gene mutation detection method. In spite of the limited number of cases investigated, our data indicate that p53 immunoreactivity and TP53 mutation analysis is not correlated to tumor progression, survival and response to treatment. CGH analysis indicates that PFTC is a genomically highly unstable type of malignancy and 3 q gain/ amplification is the major event. The frequent 3q-gains observed in HPV infected cervical carcinoma do not appear to be related to the insertion of virus DNA since all PFTC cases studied were found to be exclusively HPV negative. In conclusion, this study has confirmed that PFTC is an aggressive gynecologic malignancy which showed a high number of chromosomal aberrations comprising all chromosomes and without connection to HPV infection. This is in agreement with the high frequency (100%) of DNA aneuploid cases. None of the biological markers investigated was found to be of principal value in predicting the clinical outcome of PFTC. Only the clinical stage was found to be significantly related to patient survival.

Nyckelord

primary fallopian tube cancer, prognosis, symtoms, treatment, staging,DNA ploidy, cell proliferation, tumor angiogenesis, p53, p21WAF I expression, HPV,CGH, PCRSSCP, CDGE

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vet (ämneskategori)

dok (ämneskategori)