Prognostic value of DNA ploidy and S-phase fraction in stage I endometrial carcinoma

Citations from the literature/International Journal of Gynecology & Obstetrics 52 (19%) 325-334 cells with an anti+31 antibody revealed a band at - -1 IO-130 kDa consistentwith the known molecular massof the 81 chain, as well as severalassociatedbands consistent with noncovalently linked integrin a chains. A similar pattern of j31and c&3 integrin expression was observed for primary ovarian cancer tissue samples. Ovarian cancer cell lines exhibited significant binding to collagen type I and laminin which was primarily mediated by al integrins. In contrast, ovarian cancer cell binding to tibronectin was mediated by both a5/31and ov@3integrins. Even though mesothelial cells were observed to express libronectin mRNA and protein, binding of ovarian cancer cells to peritoneal mesothelium was not blocked by neutralizing antibodies to f31 or a~/33 integrins. These data suggest that functional integrins are commonly expressedby ovarian cancer cells, although they do not appear to mediate ovarian cancer cell implantation onto peritoneal mesothelium. The role that integrins play in the invasion of ovarian cancer cells into the submesothelial ECM deservesfurther investigation. Macrophage colony-stimulatiag factor 1, a clioically osefol tumor marker io cadomctrirl adenocarciooma: Comparison with CA 125 aad tbe amhotermloal propeptide of type III procollagen

Hakala A.; Kacinski B.M.; Stanley E.R.; Kohom E.I.; Puistola U.; Risteli J.; Risteli L.; Tomas C.; Kauppila A. AM J OBSTET GYNECOL 1995 173/l (112-I 19) OBJECTIVE: We investigated the clinical utility of macrophagecolony-stimulating factor 1 vs. CA 125and the aminoterminal propeptide of type III procollagen in endometrial carcinoma. STUDY DESIGN: Serum levels of the three substances were measured in 159 patients with untreated endometrial adenocarcinoma and in 24 patients treated with cytotoxic chemotherapy for recurrent endometrial adenocarcinema. RESULTS: Initial concentrations of colony-stimulating factor 1, CA 125,and the aminoterminal peptide of type III procollagen were above the normal range in 73%, 1I%, and 27%, respectively, of the patients. Colony-stimulating factor 1 levels correlated with those of the aminoterminal peptide of type III procollagen (r = 0.3, P = 0.002) and CA 125(r = 0.20, P = 0.036) in the total group and with those of the aminoterminal peptide of type III procollagen in stage I and II patients (r = 0.3, P = 0.0023). Colony-stimulating factor 1 levels correlated significantly with tumor grade, whereasthose of CA 125 and the aminoterminal peptide of type III procollagen correlated more closely with clinical stage. Mean colonystimulating factor 1 levels (9.6 vs. 7.7 rig/ml, P = 0.04) and the frequency of elevated CA 125 levels (3 1% vs. 8%, P = 0.048) were higher in patients with poor prognosis than in those with good prognosis. Colony-stimulating factor 1, the aminoterminal peptide of type III procollagen, and CA 125levels were useful in monitoring clinical behavior of the disease in 88%, 79%, and 63% of the cases, respectively. Levels of all three markers rose with disease progression, whereas colonystimulating factor 1 and the aminoterminal peptide of type III procollagen fell with clinical responsesto therapy. CONCLUSION: Elevated serum colony-stimulating factor 1 levels were the most accurate indicator of the presenceand activity (progression, stabilization, or regression) of primary or recurrent

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disease.Accuracy was not further enhancedby measurementof CA 125 or the aminoterminal peptide of type III procollagen levels. Progwstic value of DNA ploidy nod Spbase fraction io stage I eadcuwtrial carciooma

Ptisterer J.; Kommoss F.; Sauerbrei W.; Rendi I.; Kiechle M.; Kleine W.; Pfleiderer A. GYNECOL ONCOL 19955812(149-156) Both nuclear DNA content and s-phase fraction (SPF) can be helpful in predicting prognosis in certain malignancies. We investigated in a retrospective study the prognostic significance of nuclear DNA content and SPF as measured by flow cytometry of tumor specimensfrom 162women with nonpretreated surgically stagedFIGG stage I endometrial cancer using clearly defined inclusion criteria. A total of 139(86%)caseswere found to be diploid, whereas23 (14%)were aneuploid. Ploidy showed a correlation with histologic grade, estrogen as well as progesteronereceptor levels, and depth of myometrial infiltration. Univariate analysis of follow-up data showedan increasedrelative risk (RR) for recurrence-free survival (RFS) for grade 3 tumors (RR = 2.11, ns), for age (RR = 1.04, P = 0.023) as a continuous variable, and for SPF in diploid tumors (RR = 3.10, P = 0.035).In addition, univariate analysis of overall survival revealed similar results with a slightly increased relative risk for ploidy (RR = 1.52, ns). Multivariate analysis of RFS showed age as the only independent prognostic factor. Multivariate analysis of RFS for diploid tumors showed no independently significant factor; however, age as a continuous variable with a relative risk of 1.04and SPF with a relative risk of 2.94were of borderline significance. Our results suggestthat abnormalities of the nuclear DNA content and SPF in this homogeneousgroup of patients are associatedwith clinical and morphological prognosticators; however, ploidy is no independent prognostic factor for RFS. For diploid tumors, SPF might be a possible independent prognostic factor. Cell biological markers of drag resistance in ovarian carcinoma

Van Der Zee A.G.J.; Hollema H.H.; De Bruijn H.W.A.; Willemse P.H.B.; Boonstra H.; Mulder N.H.; Aalders J.G.; De Vries E.G.E. GYNECOL ONCOL 199558/2 (165-178) The aim of the study is to review the mechanisms of resistanceto four classesof drugs that are widely used in ovarian carcinoma: platinum (cisplatin/carboplatin) compounds, classicalalkylating agents (cyclophosphamide/melphalan), natural drugs (doxorubicin), and ‘new drugs’ (tax01 and taxotere). Both platinum and classical alkylating agents mediate their cytotoxicity by the formation of drug-DNA adducts, resulting in DNA damage.Therefore, drug resistancemechanismsare (in part) comparable. In ovarian carcinoma cell lines increasedrepair of DNA damage and increased detoxification by binding of drugs to glutathione, possibly catalyzed by glutathione Stransferases,have been identified as the most prominent resistance mechanismsto these drugs. Studies on the role of DNA repair mechanisms and glutathione in human ovarian carcinoma are hampered by the complexity of enzyme systemsin-