p53 accumulation in ovarian carcinomas and its prognostic implications.

Intranuclear p53 accumulation is a common finding in many different human tumors and is associated with a worse prognosis in breast, colon, and lung carcinomas. We immunostained a series of common epithelial ovarian cancers to assess (1) the prevalence of p53 accumulation and its clinicopathologic correlations, and (2) its prognostic implications. The study population comprised 98 patients (83 with follow-up data). A variable degree of p53 immunoreactivity, strictly confined to the neoplastic cells, was detected in 54 tumors (55%). Among these tumors there were 10 low expressors (1% to 10% immunoreactive tumor cells), 16 moderate expressors (10% to 50% immunoreactive cells), and 28 high expressors (> 50% immunoreactive cells). The prevalence of p53 immunoreactivity did not show any association with the histologic type of the tumors or with the disease stage at presentation. p53 Accumulation, however, was significantly more prevalent among poorly differentiated tumors (P = .0059, by analysis of variance). Life table analysis demonstrated that patients with tumors showing moderate and high p53 expression had worse disease-free and adjusted lengths of survival (P = .0011 and P = .0025, respectively, by Mantel-Cox). The patients with "early stage" disease (stages I and II) and p53 accumulation showed a trend toward shorter length of survival, but this did not reach statistical significance. However, patients with "advanced stage" disease (stages III and IV) and moderate or high p53 accumulation had a poorer prognosis (P = .0154 and P = .0171, for disease-free and adjusted length of survival, respectively). These results suggest that p53 accumulation occurs more frequently in tumors with aggressive behavior and that p53 immunoreactivity may have a prognostic role in certain subsets of patients with ovarian carcinoma.

Cytogenetic abnormalities and microsatellite instability in endometrial adenocarcinoma.

Recently various authors described a new mechanism involved in the genesis of some tumors, which is characterized by a tendency for replication mistakes and by genomic instability of microsatellite repeats. This instability can be revealed through the shift in the electrophoretic mobility of the analyzed fragments, which is due to a different number of repeat units. This phenomenon is widely documented in colorectal tumors of patients affected by hereditary nonpolyposis colorectal carcinoma (HNPCC). We performed a cytogenetic and molecular study of 23 endometrial adenocarcinomas to investigate the presence of genomic instability and to evaluate the possibility of a positive correlation with specific chromosomal changes. The study of genomic instability was performed using 23 microsatellites localized over 8 chromosomes. Genomic instability of microsatellites was observed in 3 cases over all 8 analyzed chromosomes. The tumoral stage of cases with microsatellite instability does not differ significantly from the remaining tumors. As a matter of fact several cases showing no evidence of instability were more advanced (II B, III A) than tumors with instability. In ten cases we observed trisomy of chromosome 10, in some as a sole anomaly. The 3 cases with genomic instability revealed a near-diploid karyotype and all showed the presence of a supernumerary marker derived from chromosome 1 rearrangements. A derivative chromosome 1 was revealed in 4 cases without evidence of microsatellite instability. It should be noted that the presence of many unidentified markers and the small number of tumors with instability do not allow us to give a definitive significance to this observation. Our results indicate that there is not an apparent correlation between microsatellite instability and specific chromosomal abnormalities. Moreover, we did not find any correlation between pathological characteristics of the tumor and genomic instability. Microsatellite instability appears to be a relatively rare event in endometrial carcinoma.

Treatment with interferon for genital HPV in HIV-positive and HIV-negative women.

The administration of interferons can be resorted to, either on its own or in combination with physical destruction methods, when the extent of genital HPV is widespread. Extensive genital HPV involvement is often seen in HIV-positive patients as a consequence of their immunodeficiency. The extension of these lesions may invalidate treatment by physical destruction, while an underlying immunodeficiency renders interferon therapy less efficacious. We studied HIV-positive and HIV-negative patients with a similar HPV involvement of their genital tract and compared the effectiveness of systemically administered alpha 2b and beta interferons in clearing HPV. Our results confirm that interferon therapy will cure most patients with extensive genital HPV when they are HIV-negative. HIV-positive patients with CD4 counts over 400 lymphocytes/mm3 may expect a similar cure rate, but this halves when this critical threshold is crossed. In these severely immunodeficient patients repeated courses of interferon therapy alone or in combination with physical destruction methods may be required to cure HPV infection.

Distribution of ceftriaxone in the tissues of the female genital system.

Twenty-nine patients, hospitalized in order to undergo gynaecological surgery involving organ removal, were treated with a single intramuscular administration of 1 g ceftriaxone before surgery. The tissue levels of the drug determined in the organs considered: uterus, ovary, fallopian tubes, vagina, proved to be comparable and to guarantee its satisfactory and uniform penetration into the tissues of the female genital system at a slowly decreasing rate. The high levels observed 12 h and 24 h after administration (2.24 +/- 0.74 mcg/g; 3.58 +/- 0.60 mcg/g; 0.70 +/- 0.45 mcg/g; 1.20 +/- 0.57 mcg/g in the ovaries and myometrium respectively) suggest a possible application of ceftriaxone in presurgical prophylaxis also in cases of female genital surgery.

[Sexually transmitted infections in patients with condylomata acuminata]. / Infezioni a trasmissione sessuale in pazienti affetti da condilomi acuminati.

42 patients (26 males, 16 females) with genital and perianal warts were submitted to serological testing for HBV markers, anti HSV antibodies and syphilis. Specimens were also collected for microscopic and cultural examination for Neisseria gonorrhoeae, Chlamydia Trachomatis, Trichomonas vaginalis, Candida albicans and other pathogenic bacteria from urethra in men and from urethra, vagina and cervix in women. Women had also cytologic examination from cervix with Papanicolau method. We have found an high incidence of urethral and vaginal asymptomatic infections, of positivity for HBV markers and some positivities of tests for syphilis. Importance of these screening examinations in the management of patients with genital warts is then discussed.

The combined evaluation of p53 accumulation and of Ki-67 (MIB1) labelling index provides independent information on overall survival of ovarian carcinoma patients.

BACKGROUND: The prognostic implications of p53 accumulation, bcl-2 immunoreactivity and tumour proliferative fraction in ovarian carcinomas are still debated. PATIENTS AND METHODS: One hundred twelve ovarian carcinomas were immunostained for p53 protein, for bcl-2 and for the cell cycle-associated Ki-67 antigen. The immunostaining results were correlated with conventional clinico-pathological variables, response to induction chemotherapy, and patient survival. RESULTS: p53 accumulation and bcl-2 immunoreactivity in more than 10% of neoplastic cells were detected in 61 (54.5%) and 42 (37.5%) cases, respectively. A positive correlation between p53 accumulation and high (more than 30% neoplastic cells) MIB1 labelling index (r = 0.235; P = 0.015) was ascertained, whereas no significant association was found between bcl-2 immunoreactivity and p53 accumulation or MIB1 labeling index. Both p53 accumulation and MIB1 immunoreactivity correlated significantly with a reduced overall survival, but the association was lost in multivariate analysis. However, patients with tumours simultaneously showing p53 accumulation and MIB1 labelling index higher than 30% had significantly reduced overall survivals, in both univariate and multivariate analyses. CONCLUSION: The simultaneous evaluation of p53 accumulation and MIB1 labelling index has independent prognostic implications in common epithelial malignancies of the ovary, irrespective of the disease stage.

Prognostic and predictive value of tumour angiogenesis in ovarian carcinomas.

Experimental studies suggest that angiogenesis plays an important role in the pathogenesis of ascites and progression of ovarian cancer. To evaluate the association of intratumoral microvessel density (IMD) with the conventional clinicopathologic features and to determine the capability of these factors in predicting responsiveness to platinum-based chemotherapy and overall survival (OS) we studied 112 ovarian carcinomas. IMD was determined using the anti-CD31 antibody and immunocytochemistry. In the entire series, we correlated IMD with the other features. In the subgroup of patients with FIGO stage III-IV (60 cases), we correlated the factors studied, determined prior of treatment, with response to therapy and prognosis. The median IMD value, in the "hot spot", in the entire series was of 48 microvessels/field. IMD values were significantly higher in mucinous carcinomas than in the other histologic types. In FIGO stage III-IV patients IMD, age and performance status (PS) were significantly associated with the probability of pathologic response to chemotherapy in univariate analysis. However, only IMD and PS retained significance in multivariate analysis. The overall capability of the 2 variables to predict response was high. In FIGO stage III-IV patients IMD, age, PS, the amount of post-operative residual disease (PORD), histologic type and response to chemotherapy were significant prognostic indicators of OS in univariate analysis. In multivariate analysis only histologic type, PORD and PS retained significance. The overall capability of these 3 variables to predict OS was satisfactory.