Patrizia Tenti

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.

Ovarian mucinous tumors frequently express markers of gastric, intestinal, and pancreatobiliary epithelial cells

In 100 mucinous tumors of the ovary (37 benign, 24 borderline, and 39 malignant), the authors determined by histochemical and immunohistochemical techniques the frequencies and patterns of expression of a total of nine markers of gastric, intestinal, and pancreatobiliary duct epithelial cells. M1, a mucin antigen, and cathepsin E (CaE), an aspartic proteinase, two markers of normal gastric superficial/foveolar epithelial cells, were expressed in 95 and 92 tumors, respectively. Periodic acid‐concanavalin A—reactive much or pepsinogen (PG) II, markers of gastric mucus neck and pyloric gland cells, were found in 79 tumors. All of these tumors also expressed M1 or CaE. DU‐PAN‐2 and the N‐terminal epitope of gastrin‐releasing peptide, markers of normal pancreatobiliary duct cells, were found in 70 and 49 tumors, respectively, and CAR‐5 and M3SI, markers of intestinal mucin, were expressed in 51 and 30 tumors, respectively. All tumors expressed at least two of the nine markers studied; none expressed PG I, a marker of gastric chief cells. The mucopeptic cell marker, PG II, was significantly more common in benign and borderline than in malignant tumors (P < 0.005), whereas CAR‐5 and M3SI, markers of intestinal mucin, were expressed significantly more often in malignant than in benign and borderline tumors (P < 0.001). By electron microscopic examination, many tumor cells had fine structural features characteristic of gastric superficial/foveolar and pyloric gland cells, intestinal columnar or goblet cells, and endocervical cells. The results indicate that gastroenteropancreatic cell differentiation—and, in particular, gastric type differentiation—is a prominent feature of ovarian mucinous tumors.

p53 OVEREXPRESSION AND HUMAN PAPILLOMAVIRUS INFECTION IN TRANSITIONAL CELL CARCINOMA OF THE URINARY BLADDER: CORRELATION WITH HISTOLOGICAL PARAMETERS

Seventy‐nine transitional cell carcinomas (TCCs) of the urinary bladder (25 grade 1, 22 grade 2, and 32 grade 3 tumours) were examined for p53 overexpression by immunohistochemistry with a monoclonal antibody and for human papillomavirus (HPV) infection by the polymerase chain reaction (PCR). Positive immunostaining for p53 was detected in 40·5 per cent of the cases; the percentage of positive cases was significantly lower in low‐grade (G1 and G2) TCCs than in high‐grade (G3) tumours (10·6 per cent vs. 84·4 per cent;P<0·0001). The overall rate of HPV infection was 32·9 per cent; 20·3 per cent of the cases were positive for HPV 16, 3·8 per cent for HPV 18, and 8·9 per cent for both. Consensus primers as well as type‐specific primers for HPV types 6, 11, and 33 failed to detect any additional case with HPV infection. The prevalence of HPV 16 and/or HPV 18 infection was significantly higher in low‐grade than in high‐grade tumours (44·7 per cent vs. 15·6 per cent;P=0·0061). p53‐positive cases were more common among papillary, deeply infiltrating tumours, and HPV‐positive cases among papillary, non‐infiltrating lesions. According to these data, p53 overexpression and HPV 16/18 infection are common findings in bladder TCC and there appears to be an inverse correlation of p53 overexpression and of HPV infection with tumour aggressiveness. The possibility of different molecular pathways in superficial low‐grade and in invasive high‐grade tumours is suggested.

Cervical Adenocarcinomas Express Markers Common to Gastric, Intestinal, and Pancreatobiliary Epithelial Cells

Frequency and pattern of expression of eight markers of gastric, intestinal, and pancreatobiliary duct epithelial cells have been investigated by histochemical and immunohistochemical techniques in 85 cases of cervical adenocarcinomas. M1, a mucin antigen, and Cathepsin E (CaE), an aspartic proteinase, markers of normal gastric superficial/foveolar epithelial cells, are expressed in 40 and 55 tumors, respectively. Periodic acid-concanavalin A-reactive mucin or Pepsinogen (PG) II, markers of gastric mucus neck and pyloric gland cells, are found in 24 tumors, 13 of which also express M1 and CaE. CAR-5 and M3SI, markers of intestinal mucin, are expressed in 68 and 12 tumors and DU-PAN-2, marker of normal pancreatobiliary duct cells, is found in 46 tumors. All but two tumors express at least one of the eight markers studied, none express PG I, marker of gastric chief cells. The different histologic subtypes of cervical adenocarcinomas expressed to a variable degree both gastrointestinal and pancreatobiliary markers. Only endocervical type tumors, however, showed the full spectrum of mucosal pyloric type differentiation, including the expression of PGII which is not present in any other histotype. A correlation between expression of gastroenteropancreatic markers and tumor grade is not apparent in our series.

Primary retroperitoneal mucinous cystoadenocarcinomas : an immunohistochemical and molecular study

Special immunohistochemical stains for the identification of gastroenteropancreatic antigens in two cases of primary retroperitoneal mucinous cystoadenocarcinomas (PRMC) show that these tumours have patterns similar to ovarian mucinous tumours. Markers of pyloric type gastric mucosa differentiation (M1, cathepsin E, concavavalin A, pepsinogen II) are mostly positive in benign and borderline areas with endocervical type differentiation, while immunoreactivity for intestinal cell markers (M3SI and CAR-5) and for DU-PAN-2 is present mainly in frankly malignant areas, regardless of differentiation type. DNA analysis shows a point mutation of K-ras oncogene at codon 12 (GGT to CGT) in one case. The immunohistochemical and genotypic similarity of PRMC and ovarian mucinous tumours may indicate similar mechanisms in their histogenesis.

Immunohistochemical localization of endothelin-like immunoreactivity in human tooth germ and mature dental pulp

SummaryThe distribution in oral tissues of endothelin, a multifunctional peptide originally identified within endothelial cells, and subsequently in some epithelial cells, neurons and neuroendocrine cells, has not been investigated yet. We have studied the localization of endothelin-like immunoreactivity in human tooth germ and mature dental pulp by immunohistochemical techniques. Such immunoreactivity was detected only within endothelial cells in both mature dental pulp and developing tooth. Arteries and veins of various sizes as well as small thin vessels displayed endothelin-like immunoreactivity. In the tooth germ, the cells of the enamel organ or the precursors of the odontoblasts were found unreactive. In the mature pulp, no cells of the stroma or nerves displayed endothelin-like immunoreactivity. These findings suggest that vascular endothelium may be the only source of endothelin in human dental tissues. It is tentatively proposed that endothelin released in mature tooth pulp may participate in the regulation of the pulpal blood flow. Although the possible role of endothelin in developing tissues is far from being clear, the mitogenic effects and the proto-oncogenes expression induced by endothelin in some cells raise the possibility that this peptide might also play a role during tooth development.

Primitive mucinous cystadenocarcinoma of the retroperitoneum case report and diagnostic considerations

The combination of ultrasonography (US) and computed tomography (CT) proved useful in recognizing and defining the characteristics of a primitive mucinous cystadenocarcinoma of the retroperitoneum, a rare anatomopathological finding which consistently presents certain macroscopic features that help in the formulation of a diagnosis with imaging techniques.

Cervical intraepithelial neoplasia in pregnant intravenous drug users infected with human immunodeficiency virus type 1

OBJECTIVE The purpose of this study was to evaluate the frequency and natural history of cervical intraepithelial neoplasia (CIN) during pregnancy in past or current intravenous drug users infected with human immunodeficiency virus type 1 (HIV-1). STUDY DESIGN We prospectively evaluated 48 pregnant HIV-1 seropositive patients and 38 HIV seronegative controls. All the subjects were current or past intravenous drug users. Follow-up visits were carried out each trimester of pregnancy and 8-12 weeks post-partum with Papanicolau smears, colposcopic examinations and, when necessary, colposcopically directed cervical biopsies. RESULTS Thirteen of 48 HIV-seropositive women (27.1%) and three of 38 HIV-seronegative controls (7.9%) (P = 0.027 by Fisher exact test) had biopsy-proven CIN at the beginning of pregnancy. High-grade CIN was detected in 10 cases (20.8%) and in two (5.3%) controls (P = 0.058 by Fisher exact test). None of the cervical squamous intraepithelial lesions progressed throughout pregnancy, in both cases and controls. Post-partum cold-knife cervical conization was performed on seven patients with CIN III and examination of the cone biopsy specimens demonstrated persistence of CIN III. CONCLUSIONS HIV-infected intravenous drug users are at high risk of CIN during pregnancy, thus requiring adequate screening programs. Our preliminary data suggest that the progression rate of CIN during gestation is low in this high-risk group.

Nucleolar organizer regions and cervical intraepithelial neoplasia among women with human immunodeficiency virus infection

OBJECTIVE Our purpose was to evaluate the proliferative activity of cervical intraepithelial neoplasia lesions in human immunodeficiency virus-seropositive women. STUDY DESIGN The proliferative activity of cervical intraepithelial neoplasia lesions was measured by nucleolar organizer regions-associated proteins count. Twenty-two biopsy specimens of cervical intraepithelial neoplasia lesions from patients positive for human immunodeficiency virus were compared with 22 matched biopsy specimens obtained from controls negative for the virus. RESULTS The mean count of nucleolar organizer regions-associated proteins per cell was 9.5 +/- 3.7 (SD) in human immunodeficiency virus-positive patients and 7.6 +/- 2.8 in human immunodeficiency virus-negative controls (p < 0.0001 by Poisson test of heterogeneity of counts). The difference in counts between the two groups, which was confirmed by log-linear analysis, persisted within each severity stratum of cervical intraepithelial neoplasia and was independent of associated human papillomavirus infection. In human immunodeficiency virus-positive patients log-linear analysis showed that high-grade cervical intraepithelial neoplasia, the presence of human papillomavirus infection, and the severity of human immunodeficiency virus disease were independently correlated with increased nucleolar organizer regions-associated protein counts per cell. CONCLUSION The results of this study indicate that the proliferative activity of cervical intraepithelial neoplasia lesions of human immunodeficiency virus-positive patients was increased compared with matched lesions from human immunodeficiency virus-negative women. This finding suggests the possibility of an increased oncogenic progression of cervical intraepithelial neoplasia lesions in human immunodeficiency virus-positive patients.

Immunogenetic Study of Women with HPV Related Cancer of the Uterine Cervix

It has been suggested that women carrying the HLA-DQ3 antigen are at increased risk of developing cervical. squamous cell carcinoma (SCC)1. Since the association between cervical. SCC and human papillomavirus (HPV) types 16 and 18 has been proved by molecular studies2 and in animal. models the tumorigenic effect of HPV may differ according to the immunogenetic background,3 the presence of a given HLA type might help linking environmental. risk factors with individual. susceptibility to cervical. SCC. Subsequent studies however have reported different findings4,5 that could be in part explained by differences in HLA phenotype among populations.