Detection of HER2 amplification using the SISH technique in breast, colon, prostate, lung and ovarian carcinoma.

HER2 gene amplification was explored using the silver stain hybridization in situ (SISH) technique in colon, prostate, lung, ovarian and breast carcinomas. Clinical pathological features and immunohistochemical (IHC) expression were evaluated for HER2 in 225 carcinomas. All cases were subjected to SISH investigation. Statistical analysis revealed an association between HER2 protein expression and gene amplification in breast carcinoma. 14% of colon carcinomas (5 IHC score 0, 1 score 1+ and 1 score 2+), 2% of prostate carcinoma (IHC 2+), 4% of lung carcinomas (IHC 2+) and 16% ovarian carcinomas (IHC 3+) revealed gene amplification. SISH is an advantageous technique for the detection of gene amplification. The use of the SISH technique in breast carcinoma may be an alternative to other in situ hybridization (ISH) techniques however more detailed studies seem necessary to detect HER2 gene amplification in other human malignancies.

Evaluation of fatty acid synthase expression in oesophageal mucosa of patients with oesophagitis, Barrett's oesophagus and adenocarcinoma.

BACKGROUND AND AIM: To evaluate the expression of fatty acid synthase (FAS) in the oesophagitis-Barrett's oesophagus-oesophageal adenocarcinoma sequence compared with p53 and Ki67 expressions, retained for a long time reliable markers of oesophageal cells biological behaviour. METHODS: In Barrett's oesophagus, oesophagitis and oesophageal adenocarcinoma patients, biopsies were taken from pathologic sites of the mucosa for histological and immuno-histochemical detection of FAS, p53 and Ki67. FAS expression was positive, when a strong granular cytoplasmic staining was observed in oesophageal cells. Ki67 and p53 was defined positive, when nuclear staining was clearly detected at 10x magnification. RESULTS: A mild expression of FAS was found in 39% of patients with oesophagitis. The amount of FAS expression increased up to 70% in Barrett's oesophagus while this was present in all patients with oesophageal adenocarcinoma (p = 0.0001). In Barrett's oesophagus, p53 was mildly or intensely expressed in 77% and in 15% of cases, respectively, and mildly or intensely expressed in 33% and 67% of patients with oesophageal adenocarcinoma, respectively, (p = 0.0001). Ki67 was mildly expressed in 17% of oesophagitis cases and was absent in the majority of cases. In Barrett's oesophagus, a mild Ki67 expression was present in 46% of cases, and in oesophageal adenocarcinoma it was present prevalently in intense form (67%; p = 0.0001). CONCLUSIONS: The over-expression of p53, Ki67 and FAS in otherwise similar morphological groups may be useful to stratify patients into selected prognostic subgroups in order to achieve better clinical approaches.

Tissue microarray analysis of FAS, Bcl-2, Bcl-x, ER, PgR, Hsp60, p53 and Her2-neu in breast carcinoma.

BACKGROUND: The aim of this study was to detect immunohistochemical markers in breast carcinoma by means of tissue microarray analysis (TMA) and to associate their expressions with clinicopathological features and prognosis. Fatty acid synthase, bcl-2, bcl-x, p53, estrogen and progesterone receptors, heat shock protein 60 and Her2-neu (c-erbB-2) were evaluated in a group of 149 breast carcinoma patients with a 5-year follow-up period. MATERIALS AND METHODS: TMA blocks were made by using duplicate 0.6-mm diameter tissue cores from each paraffin block. RESULTS: Statistical analysis revealed that tumor stage (p=0.003) and node status (p=0.001) were the only two prognostic markers of disease-free survival. Moreover, FAS and bcl-x showed an independent effect on recurrence (p=0.005). The node status was the only marker of overall survival (p=0.05). CONCLUSION: Our data confirmed recent reports associating the stage of disease, FAS and Bcl-x expressions with recurrence and outcome. These data demonstrated that TMA is an effective substitute for conventional histochemical-immunohistochemical techniques.

Overexpression of fatty acid synthase in ulcerative colitis.

Fatty acid synthase is an enzyme that catalyzes the synthesis of long-chain fatty acids. The enzyme expression is minimal in adult tissues and very high in many cancers. Ulcerative colitis is a chronic inflammatory bowel disease that, when long-standing, is associated with an increased risk of colon cancer. The aim of the present study was to establish whether fatty acid synthase levels in the mucosa without dysplasia of patients with long-standing ulcerative colitis were higher than in control subjects. Three groups of patients were selected: 30 with active ulcerative colitis, 30 with ulcerative colitis in remission, and 30 undergoing colonoscopy for colorectal cancer screening, as healthy control subjects. Fatty acid synthase expression was evaluated with immunohistochemical procedures. The enzyme was detected in all patients with active colitis, in most patients with quiescent disease, in both pathologic and normal mucosa, but in only 3 healthy control subjects. Our results suggest that extension of ulcerative colitis is greater than that revealed by common diagnostic techniques.

Fatty acid synthase is a marker of increased risk of recurrence in endometrial carcinoma.

PURPOSE: To explore the expression of fatty acid synthase (FAS) and human erythrocyte glucose transporter 1 (GLUT1) in endometrial carcinomas and to detect associations with clinicopathological features and prognosis. FAS and GLUT1 are two molecules involved in energy supply of normal cells. These markers are overexpressed in neoplastic tissues because of their increased necessity of energy. METHODS: Ninety-five patients with endometrial carcinoma were followed-up for an average period of 5 years. FAS and GLUT1 expressions were evaluated by immunohistochemistry on formalin-fixed paraffin-embedded tissues. Staining was determined with a semiquantitative method. Negative controls were obtained from patients submitted to hysterectomy for uterine prolapse. RESULTS: Eighty-five cases were endometrioid, 7 were serous, and 1 was a mucinous carcinoma. Seventy-two cases (75%) were stage I, 12 (13%) were stage II, and 11 (12%) were stage III carcinomas. Sixteen (15%) carcinomas recurred. Nine patients (8%) died for cancer during the follow-up period. FAS expression was observed in 53 cases (56%). GLUT1 expression was observed in 32 (43%) cases. Statistical analysis revealed that FAS (P = 0.04) and stage (P = 0.001) of the disease were the only two independent predictors of recurrence. GLUT1 and other clinicopathologic parameters had no prognostic association. CONCLUSIONS: FAS is a reliable marker of clinically aggressive endometrial carcinomas. The knowledge of FAS expression in endometrial carcinomas is an important finding that may stratify patients into selected groups and determine therapeutic approaches for patient care.

Fatty acid synthase (FAS) is a marker of increased risk of recurrence in lung carcinoma.

BACKGROUND: We explored the expression of Fatty Acid Synthase (FAS) in lung carcinomas and its association with clinico-pathological features and prognosis. FAS is a recently discovered molecule involved in the energy supply of normal cells. FAS is also overexpressed in neoplastic tissues because of their increased necessity for energy. PATIENTS AND METHODS: One hundred and six patients with non-small cell lung carcinoma were followed-up for an average period of 5 years. FAS expression was detected immunohistochemically. RESULTS: FAS staining was observed in 61 out of 106 cases (57.54%). Statistical analysis revealed that FAS had an overall low prognostic value (p = 0.14), while FAS-negative expression in stage I patients showed a trend for better survival (p = 0.10). PTNM stage (p < 0.0001) was the only significant prognostic marker for overall survival. CONCLUSION: FAS is a reliable marker of low-stage clinically aggressive lung carcinomas. The determination of FAS expression in lung carcinomas may stratify patients and determine therapeutic approaches for their care.

P53 as a marker of differentiation between hyperplastic and adenomatous parathyroids.

Primary hyperparathyroidism is the clinical result of parathyroid adenoma or hyperplasia, rarely of carcinoma. Clinical, serologic, and radiologic data are unable to discriminate a single parathyroid adenoma from an enlarged hyperplastic gland. Morphologic features also overlap in adenoma and small hyperplastic gland. Studying immunohistochemical expression of fatty acid synthase (FAS), p53, Ki67 and bcl-2, we found that among 21 adenomas 19 (90.5%) were positive for FAS, 12 (57.2%) for Ki67, 11 (52.4%) for p53, and 16 (76.2%) for bcl-2; among 12 hyperplasias, 12 (100%) were positive for FAS, 6 (50%) for KI67, 8 (66.7%) for p53, and 8 (66.7%) for bcl-2. Statistical analysis showed that FAS was associated with parathormone (PTH) (P =.001), Ki67 (P =.01), and p53 (P =.01). Moreover, FAS was associated with hyperplastic (P =.0001) and adenomatous glands (P =.0001). Ki67 was associated with both adenomatous (P =.02) and hyperplastic glands (P =.005). P53 protein were associated only with hyperplastic glands (P =.01). The different occurrence of p53 in parathyroids adenoma and hyperplasia may enable a different management and follow-up of the patients with primary hyperparathyroidism, stratifing them into two groups. The first, with a "false" adenoma having a high risk of relapse, may necessitate exams like serum calcium levels, PTH concentrations, urinary calcium levels for 24 hours, kidney functional tests, and radiology and ultrasound every 3 to 6 months, whereas the second with "true" adenoma, at low risk of relapse, may be checked less frequently with serum calcium levels and PTH concentrations.

Laparoscopic diagnosis and treatment of a well-differentiated papillary mesothelioma of the peritoneum.

Well-differentiated papillary mesothelioma is a rare neoplasm of peritoneum, found mainly in women of reproductive age, and usually misdiagnosed as an ovarian mass. A 46-year-old woman was clinically suspected of having an adnexal mass. Peritoneal mesothelioma was diagnosed and successfully removed at laparoscopy. Laparoscopy allows differentiation from ovarian serous tumors and treatment of the lesions. Long follow-up is recommended because of the tendency to recur.

Role and prognostic significance of CD44s expression in colorectal cancer.

UNLABELLED: The purpose of this study was to clarify the role and the predictive strength of the adhesion molecule CD44s (standard isoform) in colorectal carcinogenesis. MATERIALS AND METHODS: CD44s immunohistochemical expression was evaluated in 100 patients with colon adenoma and 100 patients with colon adenocarcinoma and adjacent non-neoplastic mucosa (ANNM). The patients were followed-up for five years. RESULTS: CD44s immunoreactivity was expressed in low-moderate-high-grade dysplasia adenomas and associated with adenocarcinoma (p = 0.01), ANNM (p = 0.05) and pTNM stage (p = 0.00001). Univariate analysis revealed that CD44s expression was associated with overall survival (OS) in carcinomas (p = 0.01) and ANNM (p = 0.05). Bivariate analysis revealed that CD44s was associated with OS in stages I and II patients (p = 0.03). Multivariate analysis revealed that stage (p = 0.0001) and CD44s expression (p = 0.05) were independent predictors of OS. CONCLUSION: CD44s is involved in colon carcinogenesis and is associated with aggressive carcinomas. The immunohistochemical expression of CD44s may reveal cells that have lost their adhesion ability and therefore detect carcinomas with high metastatic power.