Primary fallopian tube cancer

Primary fallopian tube cancer (PFTC) is a rare and aggressive gynecologic malignancyand it accounts for less than 5% of all genital female cancers according to the SwedishCancer Registry. In a retrospective study we have analysed histopathological, clinical,biological and prognostic factors among patients with PFTC. 128 cases of PFTC treatedbetween 1923 and 1991 were histopathologically reviewed and retrospectively stagedaccording 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 treatedat 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 diagnosiswas 56 years. Twenty-two per cent were suffering from salpingitis and the infertilityrate was 25%. Among the 14 variables studied in the clinical and pathological reviewand 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 changedduring the studied period. Thirty-three per cent of patients underwent surgery withtotal abdominal hysterectomy and bilateral salpingo oophorectomy. Patients receivingchemotherapy had superior survival rates (p=0.0006) and patients with cisplatinum-containingchemotherapy did better than those without. In this thesis, attempts have been made to further characterize the malignancypotential of the PFTC by biological prognostic factors. The patients in the matenalwere divided into two groups according to survival time and the interval was chosenin order to get a maximal contrast with regard to survival at a minimal cost - short-timesurvivors < 2years and long-time survivors > 8 years. We have evaluated theDNA ploidy content, proliferative activity (MIB-I), p53 overexpression combined ornot with the downstream product p21/WAF-I, and tumor angiogenesis (F8) in correlationto clinical outcome. Furthermore, we studied the frequences of p53 mutations in PFTCand in their corresponding metastases/recurrences as well as the influence of p53on therapeutic effect and clinical course in individual cases with careful clinicalfollow-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 increasedfrequency of mutations (combined p53 and p21/WAF-I) was found among short-time survivorsin stage I as well as in stage IV. Increasing MIB-I correlated to poor survival in a multivariate analysis of stageI 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 genemutation detection method. In spite of the limited number of cases investigated, our data indicate thatp53 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 malignancyand 3 q gain/ amplification is the major event. The frequent 3q-gains observed inHPV infected cervical carcinoma do not appear to be related to the insertion of virusDNA since all PFTC cases studied were found to be exclusively HPV negative. In conclusion, this study has confirmed that PFTC is an aggressive gynecologicmalignancy which showed a high number of chromosomal aberrations comprising all chromosomesand 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 foundto be of principal value in predicting the clinical outcome of PFTC. Only the clinicalstage was found to be significantly related to patient survival. Key words: primary fallopian tube cancer, prognosis, symtoms, treatment, staging,DNA ploidy, cell proliferation, tumor angiogenesis, p53, p21/WAF I expression, HPV,CGH, PCR/SSCP, CDGE ISBN 91 -628-2742-