Prospective study on prognostic significance of DNA ploidy and Ki-67 expression in colorectal cancer.

The aim of the study was to correlate tumoral DNA ploidy and Ki-67 expression with therapy response, Overall Survival (OS), Disease Specific Survival (DSS) and Disease Free Survival (DFS). Three samples of colorectal cancer were collected from each patient. One sample of normal tissue was our internal control. DNA ploidy was evaluated by FACSCalibur cytometer and Ki-67 by immunohistochemistry. We studied 67 patients and we found aneuploidy in 65,7 percent of carcinoma with a Ki-67 median expression of 55 percent. After surgery and chemotherapy in 35 percent of the patients with aneuploid carcinoma and high proliferative activity (Ki-67 greater than 55 percent) there were no evidence of disease versus 100 percent of patients with DNA diploidy and low proliferative activity (Ki-67 less than 55 percent). Tumoral aneuploidy significantly correlated with lower OS, DSS and DFS (18 percent vs 86 percent at 30 months). Univariated analysis demonstrated a significant correlation between aneuploidy and develop disease progression (p=0,033, odd ratio=5.7), while the cut-off of 55 percent for Ki-67 expression did not correlate with OS, DSS and DFS. Preliminary results (the study is still in progress) seemed to suggest that DNA ploidy has a prognostic and predictive significance in colorectal carcinoma.

Cutaneous metastasis of neuroendocrine carcinoma of the larynx: report of a case.

BACKGROUND: Cutaneous metastasis from neuroendocrine carcinomas of visceral origin is rarely described in indexed literature. The primary sites of origin include: lung (Wick et al., J Am Acad Dermatol 1985; 13: 134), larynx (Zambruno et al., Ann Dermatol Venereol 1989; 116: 855; Schmidt et al., J Laryngol Otol 1994; 108: 272; Guerzider et al., Ann Pathol 1991; 11 (4): 253), mediastinum (Yoshimasu et al., J Dermatol 2001; 28 (3): 168), uterus (Fogaca et al., J Cutan Pathol 1993; 20: 455), and thymus (Wick et al., J Am Acad Dermatol 1985; 13: 134). METHODS: In this report, the authors present the clinical, histological, immunohistochemical, and ultrastructural characteristics of secondary skin localizations of a neuroendocrine laryngeal tumor that occurred in a 61-year-old man. The complete follow up of the case is described and a brief revision of the terminology and classification of neuroendocrine neoplasms of the larynx is discussed, since a significant relationship exists between the degree of differentiation and biological behavior. RESULTS: On histological examination, the secondary cutaneous localization appeared to be more dedifferentiated compared to the primary tumor. The immunohistochemical patterns of reactivity were similar in both neoplasms, showing expression of neuroendocrine and epithelial markers. CONCLUSIONS: An important issue of prognostic significance is to differentiate a cutaneous metastasis of a neuroendocrine carcinoma from the primary small cell-undifferentiated carcinoma of the skin (Merkel cell carcinoma).

p53 codon 72 polymorphism does not affect the risk of cervical cancer in patients from northern Italy.

A case-control study was performed to investigate the risk of cervical cancer associated with p53 polymorphism at codon 72, encoding either arginine or proline. It has been recently suggested that the arginine isoform increases the susceptibility to invasive cervical cancer; however, data remain controversial. The polymorphism was examined by both allele-specific PCR and RFLP analysis in 101 patients with primary cervical cancer and in 140 healthy women of the same age and from the same geographical area. The distribution of p53 genotypes in cervical cancer patients and in controls was not significantly different (P = 0.445), and homozygosity for arginine at residue 72 was not associated with an increased risk for cervical cancer (odds ratio, 0.81; 95% confidence interval, 0.47-1.42; P = 0.52). Similarly, different genotype distribution and increased risk were not observed when patients versus controls were analyzed according to human papillomavirus status and cancer histotype. Therefore, no evidence of association between homozygosity for p53 arginine and cervical cancer was found in our population sample.

Perinatal transmission of human papillomavirus from gravidas with latent infections.

OBJECTIVE: To evaluate the risk of perinatal human papillomavirus (HPV) transmission from mothers with latent infections to the oropharyngeal mucosae of their infants. METHODS: Seven hundred eleven mother-newborn pairs were tested. Polymerase chain reaction was done with MY09/MY11 consensus primers to identify HPV DNA in maternal cervicovaginal lavages and newborn nasopharyngeal aspirates. Positive cases were further amplified with type-specific primers for HPVs 6, 11, 16, 18, and 33. All infants born to HPV-positive mothers were observed to 18 months for appearance of HPV in oropharyngeal mucosae. RESULTS: Human papillomavirus DNA was detected in 11 neonates born vaginally to HPV-positive women, a vertical transmission rate was 30% (95% confidence interval [CI] 15.9, 47). Nasopharyngeal aspirates were HPV-negative in all 11 cases in which rupture of membranes occurred less than 2 hours before delivery. When rupture preceeded delivery by 2-4 hours, and when it occurred after more than 4 hours, the respective rates for HPV positivity were seven of 21 and four of five (chi2 for trend = 10.7, P = .001). At follow-up, virus was cleared from the oropharyngeal samples as early as the 5th week. CONCLUSION: Pregnant women with latent HPV infections have low potential of transmitting the virus to the oropharyngeal mucosae of their infants. The time between rupture of the amnion and delivery seems to be a critical factor in predicting transmission. Human papillomavirus-positive infants should be considered contaminated rather than infected since virus is cleared over several months after birth.

Analysis and clinical implications of p53 gene mutations and human papillomavirus type 16 and 18 infection in primary adenocarcinoma of the uterine cervix.

Mutant p53 is frequently detected in endometrial and ovarian carcinoma, but it is rare in cervical cancers. Previous reports focused on cervical squamous cell carcinoma, whereas cervical adenocarcinoma was given little attention. We searched for p53 gene mutations in 74 primary cervical adenocarcinomas with known human papillomavirus (HPV) status. Our aim was to evaluate the prevalence of p53 mutations and to investigate their possible role as an independent prognostic factor. We found mutations in 13.5% with a high rate of G:C --> A:T transitions as observed in endometrial adenocarcinoma. As p53 mutations are more frequently detected in malignancies of high grade, high stage, and large size, this molecular event seems to play a role in the progression rather than in the induction of cervical adenocarcinoma. In our series, patients with HPV-negative tumors and patients with mutated neoplasms, irrespective of HPV infection, had a shorter survival. Yet the absence of HPV infection and presence of p53 mutations are not independent risk factors for tumor-related death after adjustment for clinicopathological confounders. The only significant and independent predictors of survival are age of patient, stage of disease, tumor grade, and presence of lymph node metastases.

Latent human papillomavirus infection in pregnant women at term: a case-control study.

Cervicovaginal lavages from 752 pregnant women at term were investigated by polymerase chain reaction to evaluate human papillomavirus (HPV) infection prevalences and were compared with cervicovaginal samples from two series of nonpregnant subjects (504 healthy women attending a family planning service and 560 symptomatic patients attending a vaginitis outpatient service). The odds ratios (ORs) of HPV infection were computed by conditional logistic regression analysis on age-matched sets. In pregnant women, the overall risk of HPV infection was about the same as in nonpregnant healthy subjects (adjusted OR, 0.90; 95% confidence interval [CI], 0.51-1.58) and was 50% less than in patients with symptomatic vaginitis (adjusted OR, 0.48; 95% CI, 0.30-0.76). Moreover, the prevalence of oncogenic HPV types 16 or 18 (or both) was lower in pregnant women (P = .015 and P = .0018 respectively).