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.

The foveolar cell component of gastric cancer.

M1, a mucin antigen, and cathepsin E, an aspartic proteinase, are both expressed in normal gastric superficial-foveolar epithelial cells. In this study, we determined by immunohistochemical staining the prevalence of these antigens in 316 gastric cancers representative of the main histologic types and stages of the disease. M1 was expressed in 201 cases (64%) and cathepsin E was expressed in 235 cases (75%) of the 313 cases investigated. Both antigens were expressed more commonly in diffuse and mixed cancers than in glandular tumors. M1 was found in 64 of 83 (77%) diffuse cancers and in 48 of 59 (81%) mixed cancers, but in only 74 of 146 (51%) glandular cancers. For cathepsin E, the prevalence was 93% in diffuse cancer, 81% in mixed cancer, and 71% in the 143 glandular cancers examined. Among 25 mucoid tumors, 15 (60%) expressed M1 but only eight (32%) expressed cathepsin E. Overall, 262 (84%) of the tumors expressed at least one of these antigens and of these, 173 (66%) expressed both antigens. No significant difference in the prevalence of M1 or cathepsin E was found between early and advanced cancer or between metastatic and nonmetastatic cancer. The two markers differed in their intracellular localization. In superficial-foveolar cells, M1 immunostaining was concentrated in secretory granules, Golgi complex, and luminal mucous, whereas cathepsin E was found in the endoplasmic reticulum. Moreover, cathepsin E, but not M1, was found in the enterocytes of duodenal villi and, occasionally, in mucopeptic cells. Parallel histochemical and ultrastructural investigations confirmed the occurrence in gastric cancer of foveolar-type cells, manifested by periodic acid-Schiff- and/or alcian blue-reactive mucous granules having a punctate substructure. We conclude that superficial-foveolar cell differentiation is common in gastric cancer and is a major component of this type of tumor. However, pure foveolar cell differentiation is rare. Rather, most gastric cancers consist of cells exhibiting features of foveolar, intestinal, and mucopeptic cell lines.

Human papillomavirus types 16 and 18 infection in infiltrating adenocarcinoma of the cervix: PCR analysis of 138 cases and correlation with histologic type and grade.

The authors investigated by PCR 138 infiltrating cervical adenocarcinoma (27 grade 1, 76 grade 2, and 35 grade 3) for the presence of human papillomavirus (HPV) 16 and 18 infection. They included 95 (68.8%) mucinous and 43(31.2%) non-mucinous tumors. The overall prevalence of HPV infection was 84.8%; 28.3% of the cases were positive for HPV 16, 29.7% for HPV 18, and 26.8% for both HPVs. Amplification of HPV 16 and 18 negative cases with consensus primers MY09/MY11 failed to yield any additional tumors with HPV DNA sequences. Patients with HPV infection were younger than the patients who were HPV-negative (P = .001). The type of HPV was unrelated to age. Human papillomavirus infection was found in 95.8% mucinous and in 60.5% non-mucinous tumors (P < .001), with even distribution among grade 1, 2 and 3 adenocarcinoma. Our findings confirm the key role of HPV 16 and 18 in the development of cervical adenocarcinoma, particularly in mucinous histotypes. The absence of HPV infection, the old age of patients and the non-mucinous differentiation may identify a subset of cervical adenocarcinoma with different etiopathogenesis.

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.

Widespread expression of intestinal markers in gastric carcinoma: a light and electron microscopic study using BD-5 monoclonal antibody.

BD-5 monoclonal antibody reacted with tumour cells in 262 of 316 cases of gastric cancers, including 121 of 134 early, 141 of 182 advanced tumours (p less than 0.01), and 113 of 146 glandular, 72 of 83 diffuse, 22 of 25 mucoid, and 55 of 59 mixed tumours. No difference in reactivity was observed between metastatic and non-metastatic advanced tumours. Immunocytochemical techniques applied to light and electron microscopical specimens of colorectal mucosa and gastric cancer showed that BD-5 immunoreactive material occurred in the Golgi complex, in small clear, to dense cored, cytoplasmic vesicles, and in the glycocalix of the luminal and lateral membranes of normal and neoplastic cells in the glands, as well as in the peripheral membrane of dispersed neoplastic cells. Mucin granules stored in the cytoplasm of goblet cells were unreactive or poorly reactive. Ultrastructural features consistent with colorectal type differentiation were observed in many reactive tumours. Unreactive tumours showing ultrastructural patterns consistent with intestinal differentiation, especially of small bowel type, were also observed. Signs of intestinal differentiation, including BD-5 immunoreactivity, often occur in gastric cancer, irrespective of histological type and stage of disease.

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.

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

The 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.

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.

Characterization of four main cell types in gastric cancer: foveolar, mucopeptic, intestinal columnar and goblet cells. An histopathologic, histochemical and ultrastructural study of "early" and "advanced" tumours.

Gastrectomy specimens of 148 gastric cancers, 40 of them being intramucosal or microinvasive, 27 penetrating the submucosa and 81 invading the muscularis propria, with or without involvement of the serosa and perigastric tissues, have been investigated with conventional histopathologic techniques, mucin histochemistry and electron microscopy to characterize the various lines of tumour cell differentiation and to correlate these with the histologic patterns of tumour growth. More or less differentiated intestinal columnar, intestinal goblet, gastric foveolar or mucopeptic cells were recognized in most tumours, of glandular, diffuse or mucoid type. Although simultaneous expression of more than one cell type into the same tumour occurred very frequently, intestinal columnar cells were more prominent in tubular adenocarcinomas, goblet cells (especially of colorectal type) in mucoid cancers, mucopeptic cells in diffuse cancers of invasive desmoplastic type and foveolar cells in diffuse cancers of intramucosal signet-ring cell type. In general, an increased tendency to foveolar cell differentiation and a reduced tendency to mucopeptic differentiation has been found in intramucosal cancers as compared to invasive cancers. It is concluded that the type of tumour cell differentiation, which might have some influence on the natural history of gastric cancer, is better related with more defined tumour subtypes than with the usually recognized glandular or diffuse patterns.

Prevalence, diagnosis and treatment of lower genital neoplasia in women with human immunodeficiency virus infection.

The prevalence of lower genital neoplasia and Human Papilloma-virus-related genital lesions were evaluated in a cohort of 75 women with Human Immunodeficiency Virus type 1 (HIV-1) infection at different stages of HIV disease. The overall rate of cervical intraepithelial neoplasia (CIN) in the group studied was 29.3% (22/75). Eight out of 10 high-grade CIN lesions contained 'high-risk' HPV-DNA 16/18 and/or 31/35/51 as demonstrated by 'in situ' hybridization with biotinylated probes. Vulvar and/or perianal condylomata were histologically diagnosed in 14 patients (18.7%); nine of these biopsies contained detectable HPV-DNA which was always related to HPV 6/11. The rate of high-grade CIN in symptomatic HIV-infected patients was 28% (7/25) as compared to 6% (3/50) of the other cases (P = 0.022). CD4 lymphocyte counts, white blood cell counts, CD4+/CD8+ cell ratio and percentage of CD4+ lymphocytes were lower in patients with high-grade CIN in comparison to the patients with negative colposcopical and/or cytological examination. After adequate standard treatment (cryotherapy, electrocauterization, cold-knife conization) only one case of CIN 2 recurred during the 2 years of follow-up period. The prevalence of lower genital neoplasia and HPV-related lesions among HIV-infected women is high and seems to correlate with the severity of HIV disease.

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.

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.

Sclerosing stromal tumour of the ovary. Ultrastructural study.

Two typical cases of sclerosing stromal tumours of the ovary are studied ultrastructurally, and the findings are correlated with the clinical data. One of the cases, with predominantly fibroblastic morphology, was asymptomatic. The second case, rich in cells with steroid-secreting features, had polymenorrhoea disappearing after removal of the tumour. The Authors suggest that clinical symptoms of sclerosing stromal tumour of the ovary depend from the degree of differentiation reached by the tumour cells.

Dedifferentiating endometrial adenocarcinoma. Report of a case.

A case of well differentiated endometrial adenocarcinoma in a 70 year-old patient is reported, which evolved to undifferentiated small cell after being treated with chemotherapy for six months. The possible mechanisms of dedifferentiation are briefly discussed.

Cytology of malignant mixed mesodermal tumour of the uterus: experience of 10 cases.

The value of cytology as a diagnostic tool in uterine MMMT has been tested in order to reach an earlier diagnosis. From 10 endocervical scrapings we were able to obtain 7 positive smears, two of them diagnostic for mixed tumour at first examination, 1 detected upon revision. In one case the positive smear was obtained from a direct scraping of the neoplasia protruding through the cervical os.

Concurrent cytogenetic and molecular investigations in uterine and ovarian neoplasms.

We studied a group of 24 uterine and ovarian neoplasms with the purpose to verify if any correlation could be established between chromosomal abnormalities, loss of heterozigosity (LOH) and microsatellite instability (MIN). Tumor specimens obtained from 24 women (12 affected by ovarian and 12 by uterine neoplasms) were split in two parts, one was used for short term cultures for cytogenetic investigation while from the second DNA was extracted for molecular studies. We studied 22 polymorphic loci from 19 chromosomes and compared the alleles observed in the tumor with those observed in the DNA obtained from peripheral blood. Extensive loss of heterozigosity was observed when total or partial chromosomal loss was observed in at least 50% of the examined cells; MIN did not correlate with any particular cytogenetic abnormality nor with LOH.

[Endometrial adenocarcinoma during the fertile age]. / Adenocarcinoma endometriale in età fertile.

Adenocarcinoma of the endometrium in patients 45 years old or younger accounts for 3-8% of all endometrial cancers diagnosed. Ten women of age = 45 years treated for endometrial cancer stage I in our Clinic of Obstetrics and Gynaecology from December 1979 to December 1988. Two cases were nulliparae, none of the 10 patients had Polycystic ovary syndrome and only was obese. In 80% of these cases the presenting symptom was abnormal vaginal bleeding and one patient had coexisting ovarian neoplasia (endometrioid carcinoma). Atypical endometrial hyperplasia was diagnosed in only one case. None of the patients had metastases or capillary like spaces invasion. Our policy was to treat these patients by hysterectomy (Piver 1 or 2), bilateral salpingo-oophorectomy and selective pelvic lymphadenectomy. One patient received adjuvant postoperative radiation therapy (49.5 Gy). One women was submitted two years later to radical mastectomy for ductal carcinoma of the breast. Endometrial adenocarcinoma in premenopausal women is generally of favourable histotype, at early stage and low grade, with excellent prognosis. The problem of quality of life is therefore of utmost importance. After surgical castration 4 of our patients experienced discomfort and excessive weight gain. The implications of long-term estrogen deprivation in younger patients must be seriously considered against as the change of ovarian conservation of hormonal replacement therapy.

The diffuse endocrine-paracrine system of the gut in health and disease: ultrastructural features.

At least 16 types of endocrine-paracrine cells have been identified ultrastructurally in the gastrointestinal mucosa. The production of hormones and local messengers such as 5-hydroxytryptamine, gastrin, cholecystokinin, somatostatin, secretin, gastric inhibitory peptide (GIP), enteroglucagon (glicentin, GLI), motilin, neurotensin, substance P and the enkephalins, by these cells, has been established. Progress has also been made in cytological studies of gut and pancreatic endocrine tumours. Argentaffin EC cell carcinoids, gastrinomas (of several ultrastructurally different varieties of gastrin cells), L-cell tumours and D-cell tumours are among those cytologically and functionally defined in the gut. Functionally undefined tumours include the so-called non-argentaffin carcinoids arising in various parts of the gut, some of which have been characterised cytologically as gastric ECL cell tumours and gastroduodenal P-D1-cell tumours. Gastrinomas, vipomas and rare argentaffin carcinoids are among gut-related pancreatic endocrine tumours. Non-functional paragangliomas, usually with some neuromatous component, occur in the duodenal wall. Extrapancreatic vipomas display ultrastructural features of ganglioneuroblastomas with peptidergic granules.

[Penile lesions induced by human papillomavirus. An immunohistochemical study and DNA hybridization]. / Lesioni peniene da papillomavirus umano. Studio immunoistochimico e con ibridazione del DNA.

Forty-nine male patients with clinically evident genital warts or suspected HPV-induced lesions detected by 5% acetic acid test were biopsied. Typical cytological and structural HPV-induced changes were observed on histological examination in 37 of 49 patients. The immunohistochemical detection of HPV capsid antigen was positive in 15 of 45 cases. In situ HPV-DNA hybridization was positive in 26 of 47 cases (24 HPV 6/11; 2 HPV 16/18). Quick blot HPV-DNA hybridization was positive in 20 of 28 cases (17 HPV 6/11 of which one positive for both HPV 6/11 and 31/33/35; 1 HPV 16/18; 2 cases positive for HPV detection, but not typed for HPV 6/11, 16/18, 31/33/35). Characteristics and use of histopathologic, immunohistochemical and HPV-DNA hybridization methods are analyzed and compared.