Double heterozygosity for BRCA1 and hMLH1 gene mutations in a 46-year-old woman with five primary tumors.

Germline mutations in BRCA1 and BRCA2 genes predispose to hereditary breast cancer, whereas carriers of mutations in any of the mismatch repair genes (MMR; hMLH1, hMSH2, hMSH6, hPMS2) are highly susceptible to Lynch syndrome. In the present study, we describe a woman affected by unilateral breast cancer at the age of 35 years. After 4 years, during the follow-up she developed synchronous (and asymptomatic) endometrial cancer, ovarian carcinoma and renal clear cell carcinoma. After 7 years (at age 46), the patient developed an infiltrating carcinoma of the contralateral breast and died in a few months of metastatic disease. Initial investigations led to the detection of a constitutional mutation in the BRCA1 gene. The extended genealogical tree disclosed a suspected history of colorectal carcinoma in the maternal branch. Endometrial cancer of the proband was investigated for microsatellite instability (MSI) and immunohistochemical expression of MLH1, MSH2 and MSH6 proteins. An high MSI status and lack of expression of MLH1 protein were detected. hMLH1 gene sequencing revealed the presence of a constitutional mutation, which was also found in the mother of the proband. Loss of the wild-type hMLH1 allele was detected in both breast tumors, thus suggesting that the MMR defect contributed to the development of the breast cancer.

A clinical-biological risk stratification model for resected gastric cancer: prognostic impact of Her2, Fhit, and APC expression status.

BACKGROUND: To obtain a prognostic stratification model for resected gastric cancer patients. PATIENTS AND METHODS: Clinicopathological and molecular data (expression of Cdx2, Apc, ß-catenin, E-cadherin, Fhit, p53, and human epidermal growth factor receptor-2 (Her2); HER2 and TOPO2A gene copy number; PIK3CA mutations; microsatellite instability) were correlated to cancer-specific/overall survival (CSS/OS) using a Cox model. Individual patient probability (IPP) was estimated by logistic equation. A continuous score to identify risk-classes was derived according to the model ratios. RESULTS: Two-hundred eight patients were studied (median follow-up 20 months). At multivariate analysis, sex, stage, margins, location, nodes, Apc, and Fhit were independent predictors for CSS; the same factors (and age and Her2, except Fhit) predicted OS. Multivariate model predicted IPP with high prognostic accuracy (0.90 for CSS; 0.91 for OS). A two-class model significantly separated low- and high-risk patients for CSS (23.4% and 85.6%, P < 0.0001) and OS (21.4% and 82.0%, P < 0.0001). A three-class model differentiated low-, intermediate-, and high-risk patients for CSS (6.3%, 35.3%, and 88.0%, P < 0.0001) and OS (6.1%, 34.6%, and 86.5%, P < 0.0001). CONCLUSIONS: A risk classification system comprising the immunohistochemical expression of three proteins (Apc, Fhit, and Her2) and five clinicopathological parameters (stage, resected nodes, margins, location, and sex) accurately separates the resected gastric cancer patients into three classes of risk.

Clinical and molecular features of attenuated adenomatous polyposis in northern Italy.

BACKGROUND: Attenuated familial adenomatous polyposis (AFAP) is characterized by the presence of 10-99 colorectal adenomas. The disease may be associated with mutations in either APC or MUTYH genes. We purposed to evaluate the contribution of adenomatous polyposis coli (APC) and MutY homologue (MUTYH) germline alterations to the AFAP phenotype and to identify genotype/phenotype correlations. METHODS: During counselling for familial adenomatous polyposis (FAP), 91 probands (and 107 affected individuals) who met the criteria of AFAP were identified. Eighty-two families were screened for constitutional mutations of the APC and MUTYH genes. RESULTS: MUTYH mutations were detected in 21 families (25.6 % of the 82 tested), and APC mutations in 7 (8.5 %). Overall, constitutional alterations were found in 34.1 % of the probands. Patients with APC mutations were younger at cancer onset and had a higher mean number of polyps (48.5 ± 33.0 in APC+ individuals vs. 35.7 ± 24.9 in MUTYH+ individuals, and 33.2 ± 18.4 in the "no mutation" group). Clinical features rendered the "no mutation" group closer to MUTYH+ than to the APC+ group. Colorectal cancer at diagnosis was detected in 40 % of AFAP individuals. CONCLUSIONS: AFAP is a new clinical entity with its frequency in the general population still undefined. The number of adenomas varies greatly, with an average of 30-40 lesions. The molecular basis of AFAP can be established in approximately 1/3 of the patients. Both MUTYH and APC genes are implicated in AFAP, though the role of MUTYH is of considerably greater relevance.

A mononucleotide markers panel to identify hMLH1/hMSH2 germline mutations.

Hereditary NonPolyposis Colorectal Cancer (Lynch syndrome) is an autosomal dominant disease caused by germline mutations in a class of genes deputed to maintain genomic integrity during cell replication, mutations result in a generalized genomic instability, particularly evident at microsatellite loci (Microsatellite Instability, MSI). MSI is present in 85-90% of colorectal cancers that occur in Lynch Syndrome. To standardize the molecular diagnosis of MSI, a panel of 5 microsatellite markers was proposed (known as the "Bethesda panel"). Aim of our study is to evaluate if MSI testing with two mononucleotide markers, such as BAT25 and BAT26, was sufficient to identify patients with hMLH1/hMSH2 germline mutations. We tested 105 tumours for MSI using both the Bethesda markers and the two mononucleotide markers BAT25 and BAT26. Moreover, immunohistochemical evaluation of MLH1 and MSH2 proteins was executed on the tumours with at least one unstable microsatellite, whereas germline hMLH1/hMSH2 mutations were searched for all cases showing two or more unstable microsatellites. The Bethesda panel detected more MSI(+) tumors than the mononucleotide panel (49.5% and 28.6%, respectively). However, the mononucleotide panel was more efficient to detect MSI(+) tumours with lack of expression of Mismatch Repair proteins (93% vs 54%). Germline mutations were detected in almost all patients whose tumours showed MSI and no expression of MLH1/MSH2 proteins. No germline mutations were found in patients with MSI(+) tumour defined only through dinucleotide markers. In conclusion, the proposed mononucleotide markers panel seems to have a higher predictive value to identify hMLH1 and hMSH2 mutation-positive patients with Lynch syndrome. Moreover, this panel showed increased specificity, thus improving the cost/effectiveness ratio of the biomolecular analyses.

Cell kinetic evaluation of human colonic aberrant crypts. (Colorectal Cancer Study Group of the University of Modena and the Health Care District 16, Modena, Italy).

Foci of aberrant crypts (ACF) have been observed on the unsectioned, methylene blue-stained mucosal surface of the human colon. Experimental evidence and the histological features of the lesions suggest that they might be early events in colon cancer development. The main objective of the present study was to evaluate cell kinetic properties of ACF in the human colon. Five samples of colon mucosa were collected immediately after operation following the administration of 500 mg of 5'-bromo-2'-deoxyuridine prior to surgery. ACF were then identified on the fixed, unsectioned, methylene blue-stained mucosal surface under a light microscope. Some specimens containing ACF were serially sectioned perpendicular to the luminal surface of the intestine, along with specimens of normal-appearing mucosa. Several sections were prepared for the immunohistochemical identification of 5'-bromo-2'-deoxyuridine-incorporating cells (in the S phase of the cell cycle). The results of this study demonstrated that aberrant crypts have more cells per crypt than normal glands. Total labeling index and labeling index values in each of the five longitudinal compartments in which each crypt was divided showed an increased total proliferative activity in all ACF examined, although limited to the lower crypt compartments in almost all aberrant crypts evaluated. These findings are in keeping with previous cell kinetic studies and observations in experimental animals and provide evidence of the involvement of human aberrant crypts in the stepwise process leading from normal mucosa to colon cancer.

Microsatellite instability and mismatch-repair protein expression in hereditary and sporadic colorectal carcinogenesis.

Aberrant crypt foci (ACF) are microscopic clusters of altered colonic crypts considered premalignant lesions in the large bowel. Genomic instability at short tandem repeats in the DNA, referred to as microsatellite instability (MSI) is the hallmark of hereditary nonpolyposis colorectal carcinoma (HNPCC) caused by mutations in DNA mismatch-repair genes, mostly hMLH1 and hMSH2. In this study, we evaluated for MSI ACF (n = 16), adenomas (n = 18), carcinomas (n =22), and lymph node metastases (n = 3) from 17 patients with colorectal cancer positive for MSI. Ten patients were members of HNPCC families; 7 patients had no family history of cancer. MSI was found in 7 of 7 (100%) ACF and 11 of 12 (91%) adenomas from patients with HNPCC. MSI was not related to histology and size of ACF. A progressive increase in instability as estimated by the number of shifted bands was observed along the ACF-adenoma-carcinoma sequence. In contrast, two of nine (22%) ACF and none of six adenomas from patients with MSI sporadic carcinoma were unstable at microsatellite loci. hMLH1 or hMSH2 protein expression was altered only in MSI-positive premalignant lesions (ACF and/or adenomas), but not in all MSI-positive lesions in patients with HNPCC. These observations provide evidence of the premalignant nature of ACF in HNPCC and suggest that MSI is a very early event both in HNPCC and in sporadic colorectal carcinogenesis, although in the latter it seems infrequent.

Molecular screening for hereditary nonpolyposis colorectal cancer: a prospective, population-based study.

PURPOSE: Germline mutations in mismatch repair genes predispose to hereditary nonpolyposis colorectal cancer (HNPCC). To address effective screening programs, the true incidence of the disease must be known. Previous clinical investigations reported estimates ranging between 0.5% and 13% of all the colorectal cancer (CRC) cases, whereas biomolecular studies in Finland found an incidence of 2% to 2.7% of mutation carriers for the disease. The aim of the present report is to establish the frequency of the disease in a high-incidence area for colon cancer. PATIENTS AND METHODS: Through the data of the local CRC registry, we prospectively collected all cases of CRC from January 1, 1996, through December 31, 1997 (N = 391). Three hundred thirty-six CRC cases (85.9% of the incident cases) were screened for microsatellite instability (MSI) with six to 12 mono- and dinucleotide markers. MSI cases were subjected to MSH2 and MLH1 germline mutation analysis and immunohistochemistry; the methylation of the promoter region was studied for MLH1. RESULTS: Twenty-eight cases (8.3% of the total) showed MSI. MSI cases differed significantly from microsatellite-stable (MSS) cases for their proximal location (P <.01), high mucinous component (P <.01), and poor differentiation (P =.002). Of MSI cases studied (n = 12), only one with a family history compatible with HNPCC had a germline mutation (in MSH2). Five other patients with a family history of HNPCC (two with MSI and three with MSS tumors) did not show germline mutations. CONCLUSION: We conclude that the incidence of molecularly confirmed HNPCC (one [0.3%] of 336) in a high-incidence area for CRC is lower than in previous biomolecular and clinical estimates.

Frequency and type of colorectal tumors in asymptomatic high-risk individuals in families with hereditary nonpolyposis colorectal cancer.

In hereditary nonpolyposis colorectal cancer (HNPCC, or Lynch syndrome) a close surveillance is usually proposed to high-risk family members with the ultimate goal of reducing cancer incidence and mortality. Through a specialized registry, between 1984 and 1996, we identified 31 families with clinical features of HNPCC. A total of 390 first-degree relatives of affected patients were considered at high risk for colorectal cancer. The main purposes of this study were: (a) to assess overall compliance; and (b) to evaluate the frequency and morphological features of tumors detected at endoscopy. Two hundred twenty-three subjects could be directly interviewed and colonoscopy strongly recommended. Each of the 86 individuals who underwent colonoscopy was matched to a control of the same age (+/-3 years) and sex (control subjects were seeking endoscopy for constipation, rectal bleeding or abdominal discomfort). Of the 390 individuals traced as "at risk," 223 (57.2%) could be contacted, and, of these, 86 (38.6%, or 22.0% of the total) underwent colonoscopy. One or more colorectal lesions were found in 35 of 86 (40.7%) HNPCC asymptomatic family members and in 15 (17.4%; P < 0.001) controls. In the former group, 29 adenomas were detected in 20 individuals as opposed to 11 adenomas in 9 subjects among controls (P < 0.03). Moreover, adenomas in family members were significantly larger [9.1 +/- 5.9 mm (mean +/- SD) versus 5.8 +/- 3.7 mm; P < 0.02] and more frequently showed a tubulovillous histological type and a high degree of dysplasia. Five colorectal carcinomas (in four patients) were detected among cases (four of which were located between the cecum and the hepatic flexure); only one was detected among controls. Surveillance of high-risk subjects in HNPCC families can be carried out only in a fraction of them, because the majority cannot be reached or refuse to collaborate. On the other hand, the frequency of newly detected lesions among family members and the possible aggressive behavior of the lesions render pancolonoscopy necessary at regular intervals of time.

Clinical features, frequency and prognosis of Dukes' A colorectal carcinoma: a population-based investigation.

The main aim of this study was, through the data of a population-based Registry, to establish the incidence of Dukes' A lesions by year of registration and the main clinical features, and to assess cancer-specific survival. One hundred and eighteen Dukes' A colorectal tumours were diagnosed (in 117 patients) out of 1337 registered between 1984 and 1992 in the Health Care District of Modena, Northern Italy; 94 patients were treated with surgery and 23 with endoscopic polypectomy. The frequency of Dukes' A tumours ranged between 4.8% and 18% by year of registration. Dukes' A carcinomas were significantly more frequent in the distal colon. Only 5 patients (4%) died of their cancer, and in all patients the tumour was localised in the rectum. Carcinomas associated with a poor prognosis did not show any of the biological variables usually associated with an unfavourable outcome, but, our data suggest the possibility of incomplete removal of tumours at surgery.

Descriptive epidemiology of colorectal cancer in Italy: the 6-year experience of a specialised registry.

The Colorectal Cancer Registry of Modena recorded 838 malignancies of the large bowel between 1984 and 1989. Crude Incidence rates were 59.5 new cases per 100,000 per year in men and 47.4 in women (age-standardised values 33.1 and 20.6, respectively). 35 incident cases (4.2%) had multiple colorectal tumours, whereas 42 (5.1%) had extraintestinal malignancies (mainly breast, endometrium and stomach). Although 90.5% of the patients underwent surgery, this was "curative" in 634 (77.6% of the total), while 105 individuals (12.8%) had palliative operations; 78 patients (9.5%) were not operated, mainly because of metastatic disease or poor clinical condition. Finally, emergency operations--due to intestinal obstruction, perforation or massive bleeding--were carried out in 46 patients (6.1%). A total of 659 tumours (79%) were accurately staged. Among first-degree relatives of the registered patients a significant excess of cases of colorectal cancer was found in each year of the study. 5-year survival was evaluated in 132 (out of 140) patients registered in 1984 and followed-up until 1989. Overall 5-year survival was 37%, but rose to 43% when only colorectal cancer related deaths were taken into consideration. As expected, survival was strongly influenced by stage (P < 0.0001 by log-rank test). In conclusion, this study confirms previously reported data about incidence and mortality rates for colorectal cancer in northern Italy. The particular approach--limited to the large bowel--allowed the evaluation of the frequency of multiple tumours and of the marked aggregation of cancer among first-degree relatives. Finally, survival figures are comparable to those of many other studies and confirm that the clinical outcome of this neoplasm remains unfavourable in more than 50% of the affected patients.

Survival for colon and rectal cancer in a population-based cancer registry.

Dukes' stage is the most powerful indicator of patient outcome for colorectal cancer. Several cancer survival studies have considered other prognostic variables, but results are often conflicting. We sought to assess the independent value of several clinical and morphological variables in defining colorectal cancer specific survival. 397 colorectal cancer patients diagnosed from 1984 to 1986, and registered in a large bowel cancer registry instituted in a local health district of Northern Italy, were actively followed-up until 31 December 1991. Univariate and multivariate survival analyses were carried out in colon and rectal cancer cases, separately, using the actuarial life-table method and Cox proportional hazard regressions. Crude and specific 5-year survival rates were 37.5 and 41.4%. In univariate analysis, TNM (tumour, nodes and metastases) stage was the strongest predictor of prognosis in both sites. Other variables significantly related to survival were age of patient at diagnosis and pattern of tumour growth in colon cancer, type of differentiation and pattern of tumour growth in rectal cancer. In multivariate analyses, after adjusting for stage, age had a weak but significant negative effect on colon cancer survival, whereas rectal tumours with the infiltrating type of growth had a significantly worse prognosis than those with the expanding type. Colorectal cancer survival should be analysed in the main large bowel subsites in order to define high-risk groups within each TNM stage category.

Biologic characterization of hereditary non-polyposis colorectal cancer. Nuclear ploidy, AgNOR count, microvessel distribution, oncogene expression, and grade-related parameters.

The identification of hereditary non-polyposis colorectal cancer (HNPCC) is important not only for the patient, but also for family members who are at increased risk of developing cancer. To determine if measuring various pathobiologic features of the colon carcinomas is useful in separating sporadic from HNPCC tumors, the authors studied tumor tissues from 46 patients with HNPCC and compared them to 70 with sporadic colorectal carcinoma. Parameters investigated included DNA ploidy (flow cytometry), AgNOR count (by silver staining), microvessel density (immunohistochemistry), p53 and K-ras expression, and grade-related parameters. Diploid tumors were more frequent in patients with HNPCC (65% vs 40%, P < .02), thus confirming previous observations concerning such an association. Higher AgNOR counts and greater AgNOR areas were observed in sporadic tumors than in HNPCC (5.2 +/- 1.5 vs 4.5 +/- 1.8, P < .01). Hereditary tumors tended to be less vascularized, whereas oncogene expression and grade-related parameters did not show appreciable differences between the two types of tumors. In conclusion, some of the investigated parameters may contribute to defining the biologic profile of HNPCC. In addition, these findings support the clinical impression of a more favorable outcome that is frequently seen in HNPCC patients.

Mental nerve invasion by basal cell carcinoma of the chin: a case report.

A case of perineural infiltration from recurrent cutaneous basal cell carcinoma of the chin is reported. Clinical presentation, surgical treatment, and pathological evidence are discussed. This report stresses the importance of a correct follow-up and an accurate clinical staging in order to identifying clinical signs highly suspicious for neoplastic perineural infiltration.

Perineural infiltration by cutaneous squamous cell carcinomas of the head and neck.

In this paper six cases of cutaneous squamous cell carcinoma of the head and neck region with histologically-documented perineural tumoral infiltration are presented. Most patients showed recurrent disease during follow-up and have been treated with surgery and radiotherapy with or without systemic chemotherapy. The prognostic implications of perineural neoplastic infiltration as well as of therapeutic options are discussed.

Pathology of colorectal cancer.

The earliest phases of colorectal tumourigenesis initiate in the normal mucosa, with a generalised disorder of cell replication, and with the appearance of clusters of enlarged crypts (aberrant crypts) showing proliferative, biochemical and biomolecular abnormalities. The large majority of colorectal malignancies develop from adenomatous polyps. These can be defined as well demarcated masses of epithelial dysplasia, with uncontrolled crypt cell division. An adenoma can be considered malignant when neoplastic cells pass through the muscularis mucosae and infiltrate the submucosa. Definitions like "carcinoma in situ" or "intramucosal carcinoma" should be abandoned, since they lead to confusion. Although several lines of evidence indicate that carcinomas usually originate from pre-existing adenomas, this does not imply that all polyps undergo malignant changes, and does not exclude "de novo" carcinogenesis. Besides adenomas, other types of polypoid lesions include hyperplastic polyps (showing elongated crypts often with cystic dilatation), serrated adenomas (with a serrated glandular pattern], flat adenomas (flat lesions which are difficult to detect in routine lower endoscopy, but may possess malignant potential), hamartomatous polyps (which show a complex branching pattern of smooth muscle supporting normal lamina propria and glands), and inflammatory polyps. Colorectal carcinomas are one of the most frequent neoplasms in Western society; the macroscopic appearance of these lesions may be that of a polypoid vegetating mass or of a flat infiltrating lesion. Most of these tumours are adenocarcinomas (96%), that, in some cases, show a mucinous component. More rare malignancies of the large bowel include signet-ring cell carcinoma, squamous carcinoma, undifferentiated neoplasms and medullary type adenocarcinoma (solid carcinoma with minimal glandular differentiation or slight cellular pleomorphism). Colorectal carcinoma can be graded into well, moderately and poorly differentiated lesions; there is little evidence, however, that grading may be of help in evaluating prognosis of affected patients. In conclusion, colorectal tumours cover a wide range of premalignant and malignant lesions, many of which can easily be removed at endoscopy. It follows that colorectal neoplasms might be prevented by interfering with the various steps of carcinogenesis, which begins with uncontrolled epithelial cell replication, continues with the formation of adenomas of various dimensions, and eventually evolves into malignancy.

Staging and survival of colorectal cancer: are we making progress? The 14-year experience of a Specialized cancer Registry.

BACKGROUND AND AIMS: It is still unclear whether recent advancements in colorectal cancer research have led to an improvement in management and prognosis of the disease. Through the data of a specialized colorectal cancer Registry we aimed at analysing pathological staging and 5-year survival of all patients with malignancies of large bowel diagnosed between 1984 and 1997. Main objective was to ascertain whether or not we are making progress in the control of this common neoplasm. PATIENTS AND METHODS: During the 14-year period 1984-97, a total of 2,240 colorectal cancer patients were registered, for a crude incidence rate of 64.5 and 55.2/100,000/year in males and females, respectively Tumours were staged with "Tumour, Node, Metastasis" system, corresponding to Dukes' classification, into four main groups. Survival was assessed with Life Table analysis, and statistical significance--between various subgroups--evaluated with Log-Rank Test. RESULTS: Crude incidence rates of colorectal neoplasms showed minor fluctuations during initial period of registration, increasing sharply after 1990 mainly due to localized (stage I and II) lesions and, to a lesser degree, to stage III tumours. Number of advanced (stage IV and unstaged) malignancies remained virtually stable. When results were expressed as percent of total cases, the fraction of localized lesions increased from 39% in the biennium 1984-5 to 51.6% in 1986-97, and the proportion of advanced tumours fell from 39% to 21.6% (p for trend <0.001). As expected, 5-year survival was significantly (p<0.002) more favourable for individuals diagnosed in 1990-91 than for patients registered in 1984-89. CONCLUSIONS: In Northern Italy, incidence rates of colorectal carcinoma are rising. This trend is associated with a sharp increase of newly detected localized lesions and with a significant improvement of overall 5-year survival. The result may be attributed to several concomitant factors, such as: A] wider use of colonoscopy, B) increased education of patients, C) more attention given to symptoms.

Vinorelbine plus cisplatin in recurrent or previously untreated unresectable squamous cell carcinoma of the head and neck.

Despite considerable progress achieved in the management of head and neck carcinomas (HNC) in the last decade, the prognosis of patients with advanced squamous cell HNC is still dismal. On the basis of the reported good activity of a new vinca alkaloid derivative, i.e., vinorelbine (VNR), we tested the combination of cisplatin and VNR in a series of patients with recurrent or previously untreated unresectable squamous cell HNC. Thirty-five patients with recurrent or previously untreated unresectable squamous cell HNC were treated with a combination of cisplatin 80 mg/m2 on day 1, plus vinorelbine 25 mg/m2 i.v. push on days 1 and 8. This cycle was repeated every 3 weeks. Analysis of response rates was carried out separately for previously untreated patients, and those with recurrent disease after surgery and/or radiotherapy. In the group of 20 patients with recurrent disease the overall response rate was 55% (95% CL 44-66%), with 3 patients (15%) showing a complete response with a mean duration of 6.2+ months and 8 patients showing a partial response with a mean duration of 8.6+ months. In the group of patients with previously untreated unresectable disease, 13 patients (87%, 95% CL 78-96%) had a major objective response with a complete response rate of 27%. This regimen was quite well tolerated, with meyelosuppression and vomiting being the most frequent toxicities. The occurrence of an acute pain syndrome following vinorelbine administration in 4 patients is noteworthy. In conclusion, this combination is active in advanced squamous cell head and neck carcinoma. However, although it may be recommended in recurrent carcinoma, the complete response rate achieved in previously untreated patients is lower than that reported with other more intensive regimens.

Expression of p53 protein in prostate cancers of different histologic types.

Mutations and overexpression of p53 gene in prostate carcinoma have been found but their significance in the development and progression of cancer is so far unknown. We investigated the prevalence of abnormalities of p53 protein in a heterogeneous group of prostate carcinoma to verify whether acinar and non acinar carcinomas have a different expression of p53 protein. Paraffin sections of 45 prostate carcinomas (39 acinar, 3 ductal papillary, 1 transitional cell, 1 mucinous and 1 pure small cell) were examined for the expression of p53 protein using a panel of antibodies (monoclonal antibodies Pab 1801, D07 and polyclonal antibody CM1). No p53 expression was observed in any acinar carcinomas independent of grade and stage. For non acinar carcinomas only small cell and transitional cell carcinomas exhibited detectable amounts of p53 protein in tumour cell nuclei. The prevalence of p53 overexpression in prostate carcinoma is relatively low compared with that found in many other tumours. In the present study, the overexpression of p53 in a small cell carcinoma and in a transitional cell carcinoma suggest that the loss of suppressing role of p53 gene may be an important mechanism in the genesis and in the development of these uncommon tumours.

Acanthamoeba meningoencephalitis in a patient with acquired immunodeficiency syndrome.

Several cases of Acanthamoeba encephalitis (ie, granulomatous amebic encephalitis) have been reported in patients with acquired immunodeficiency syndrome from the United States. To our knowledge, none so far has been reported from Europe, and this is the first case of amebic meningoencephalitis due to Acanthamoeba in a patient with acquired immunodeficiency syndrome from Italy. The patient was a 24-year-old, human immunodeficiency virus-positive heterosexual man with a 6-year history of intravenous drug use. He was admitted to the hospital because of severe headache, confusion, nuchal rigidity, jaundice, and ascites. He died 5 days later. At autopsy, the brain showed extensive hemorrhagic necrosis with numerous trophic and cyst forms of Acanthamoeba. The amebas were identified as Acanthamoeba divionensis by the indirect immunofluorescence test.

[Leiomyoblastoma of the stomach. Another case report]. / Leiomioblastoma dello stomaco. Ulteriore contributo casistico.

A further case of gastric leiomyoblastoma in a 53 year old woman is presented. Pathology, diagnosis, and therapy of this rare neoplasm are discussed.