Immunohistochemical expression of fatty acid synthase, Ki-67 and p53 in squamous cell carcinomas of the larynx.

Fatty acid synthase (FAS) is a recently discovered molecule involved in the energy supply to normal cells. FAS is overexpressed in neoplastic tissues because of their increased energy needs. We explored the immunohistochemical expression of FAS, Ki-67 and p53 in squamous cell carcinomas (SCC) of the larynx and their association with clinicopathological features and outcome. Specimens from 43 patients with SCC were evaluated. Statistical analysis revealed an association between poorly differentiated laryngeal carcinomas and FAS expression (p<0.005) and between FAS and Ki-67 overexpression (p<0.001). Finally, FAS expression was associated with overall survival (p<0.001). We suggest that FAS is a powerful prognostic indicator whose strength can be enhanced when it is evaluated together with clinicopathological data and Ki-67 expression.

Asymptomatic struma ovarii: a case report.

Struma ovarii is a rare ovarian neoplasm. This tumor is generally benign, although malignant transformation has been reported. The preoperative diagnosis is generally difficult. Thyroid hormones may be produced and in a few cases asymptomatic women may develop definitive clinical hypothyroidism after resection of struma ovarii. We report a case of a 39-year-old woman who underwent laparoscopic resection of an asymptomatic right ovarian mass. The pathologic diagnosis was struma ovarii. The postoperative period was uneventful and her thyroid function remained normal.

Fatty acid synthase expression in melanoma.

BACKGROUND: Fatty acid synthase (FAS), the key enzyme responsible for the synthesis of fatty acids, is weakly expressed in some normal human tissues. Recently, FAS has been demonstrated to be overexpressed in many non-neoplastic highly proliferative lesions and in aggressive carcinomas with poor outcome, including colon, breast and ovary carcinomas. METHODS: In order to evaluate the prognostic significance of FAS in human melanoma, we analysed by means of immunohistochemistry, using a monoclonal anti-FAS antibody, 77 primary melanomas and 30 nodal and cutaneous metastasis. Thirty nevi (15 dermal and 15 junctional nevi) were used as controls. All patients were followed-up for 5 years. RESULTS: Thirty-four melanomas expressed strong FAS immunostaining; the remaining 43 cases showed weak expression or were negative. All cutaneous and nodal metastasis were strongly positive. All patients with metastases deceased during the follow up period. Control specimens expressed weak staining. None of these patients developed recurrence. Statistical analysis revealed significant association of FAS expression with Breslow thickness (p = 0.012). The intensity of FAS immunostaining was also predictive of prognosis (p = 0.049). CONCLUSIONS: FAS is a reliable prognostic marker in human melanomas. FAS predictive strength is increased when associated with Breslow thickness. The observation of FAS in human melanomas may stratify patients for stricter follow-ups and suggest different therapeutic approaches.

Abnormal "low grade" transformation zone: current diagnostic gold standard.

The aim of this work was to examine different methods of investigation in the diagnosis of the abnormal "low grade" transformation zone of the portio. Over a period of one year 41 patients subjected to colposcopic examination underwent exo-endocervical sampling for oncologic evaluation and for detection of viral and bacterial infections (HPV, HSV, adenovirus, mycoplasmas and chlamydia trachomatis), as well as portio biopsy. A 65.8% correlation was found between cytology and the HPV-DNA test results, while histology and the presence of the HPV virus agreed in 51.4% of cases. In those cases in which minimal histological alterations were found (koilocytosis) a high percentage of HPV negativity was found. In discordant negative cytologic tests that were however positive for HPV by PCR, the genotypes identified were always 6 and 11.

Immunohistochemical expression of human erythrocyte glucose transporter and fatty acid synthase in infiltrating breast carcinomas and adjacent typical/atypical hyperplastic or normal breast tissue.

To evaluate the immunohistochemical expression of GLUT1, human erythrocyte glucose transporter 1, and fatty acid synthase (FAS), 66 human breast carcinomas and adjacent peritumoral tissue were studied. GLUT1 and FAS were expressed in 53 and 61 carcinomas, in 17 and 14 typical/atypical hyperplastic tissues, and in 16 and 13 tissues adjacent to tumor normal breast tissue, respectively. Statistical analysis revealed association between invasive carcinomas, invasive carcinomas with in situ component and GLUT1 immunostaining. GLUT1 staining was associated with tumor grade, FAS with tumor stage, and GLUT1 and FAS coexpression with tumor grade. Controls expressed no immunostaining. GLUT1 and FAS are new markers involved in the biologic activities of cancer cells. GLUT1 and FAS coexpression may indicate increased use of energy by the neoplastic cells correlated with poorly differentiated features and aggressive behavior. The innovative finding that GLUT1 and FAS are observed in mammary carcinoma adjacent nonneoplastic tissues may suggest a role in detecting initial phases of breast carcinogenesis.

[Malignant phyllode tumor of the breast with features of intraductal carcinoma]. / Tumore filloide maligno della mammella con aspetti di carcinoma intraduttale.

Malignant phyllode tumor is a rare biphasic breast tumor consisting of a malignant mesenchymal component and an epithelial component that is usually benign. We report an unusual case of a malignant phyllode tumor of the breast with neoplastic features of both the epithelial and stromal components. The patient was a 39-year-old woman with family history for breast carcinoma. Grossly, the excised tumor was a 9 x 7 x 5.5 cm gray lobulated mass with infiltrative margins and necrotic-hemorrhagic areas. Histologically the tumor consisted mainly of neoplastic mesenchyme with non invasive comedo, cribriform and micropapillary features of the ducts. Three months after the excision of the neoplastic mass, the patient developed an infiltrating ductal carcinoma of the opposite breast. Hereditary and bilateral tumors are commonly associated with germline mutations. Tissue from both neoplasms however did not express either BRCA1 or BRCA2 mutations.

Immunohistochemical study of fatty acid synthase in ovarian neoplasms.

In order to evaluate the prognostic significance of fatty acid synthase (FAS), the key enzyme in fatty acid biosynthesis, in ovarian benign and malignant tumors 98 patients with ovarian masses were immunohistochemically evaluated. Histologic features of the lesions and expression for FAS were statistically associated with clinical data and disease-free survival over a 5-year follow-up period. The mean age of patients was 65 years. TNM surgical stages were I in 31.8%, II in 28.2% and III in 40% of cases. The 5-year disease-free survival of the 85 malignant common epithelial ovarian tumors was 47.1% while 35.3 of patients died with active disease. Seventy-eight (79.6%) out of 98 cases expressed FAS in the neoplastic epithelial cells and 42 (42.9%) in the non-neoplastic stromal cells. Statistical analysis revealed FAS expression and stage of the disease to be significantly correlated to recurrence and survival rates only in the malignant common epithelial tumors. Moreover, multivariate analysis showed FAS expression (p=0.05) and tumor stage (p=0.03) to be independent prognostic predictors. FAS is a reliable predictor of recurrence and disease-free survival in common epithelial ovarian tumors along with neoplastic stage. Clinical data, other histologic subtypes and grading were not statistically significant.

Immunohistochemical study of fatty acid synthase, Ki67, proliferating cell nuclear antigen, and p53 expression in hyperplastic parathyroids.

Patients with secondary hyperparathyroidism following chronic renal disease frequently develop hyperplastic parathyroids. Hyperplastic parathyroids have an increased number of chief cells, a decreased amount of stromal fat, and a nodular or diffuse histologic pattern. Hyperplastic parathyroids may also express higher proliferative activity compared with controls. We evaluated the morphologic features and immunohistochemical expression of fatty acid synthase (FAS), Ki67, proliferating cell nuclear antigen, and p53 protein in 78 hyperplastic parathyroids from 20 patients with secondary hyperparathyroidism. Twenty normal parathyroids incidentally removed during nonneoplastic thyroid surgery were used as controls. Our results showed that hyperplastic glands overexpress FAS (P =.06). Statistical analysis also revealed a significant association between FAS and p53 protein (P =.006) and between FAS and hyperplastic glands with a predominant nodular pattern (P =.02). Hyperplastic parathyroids from patients with chronic renal failure strongly express FAS. Fatty acid synthase may therefore be a potential biological indicator of highly proliferating parathyroid cells.

Fatty acid synthase (FAS) predictive strength in poorly differentiated early breast carcinomas.

AIMS AND BACKGROUND: Many normal and human cancer tissues express fatty acid synthase (FAS), the major enzyme required for endogenous fatty acid biosynthesis. Strong expression of FAS seems to be associated with a poor prognosis. This study examines the strength of FAS and other common markers of relapse in poorly differentiated breast carcinoma. MATERIALS AND METHODS: Fifty-one patients with poorly differentiated ductal infiltrating breast carcinomas were followed up for more than 10 years. Immunohistochemical detection of FAS was associated with morphological features of the tumors, with immunohistochemical expression of c-erbB-2, cathepsin D, estrogen and progesterone receptor status and with DNA ploidy in order to detect a statistical correlation. RESULTS: The chi-square test revealed a correlation between FAS and peritumoral lymphatic vessel invasion (PLVI) (P = 0.001). Univariate analysis showed that FAS was correlated with disease-free survival (DFS) (P = 0.0001). Other prognosticators associated with DFS were PLVI (P = 0.002), estrogen (P = 0.008) and progesterone receptor status (P = 0.007). Bivariate analysis showed that FAS was a further prognostic discriminant of DFS within the ER, PgR and PLVI subsets. DISCUSSION: FAS is a reliable prognosticator of recurrence in poorly differentiated early breast carcinomas. Association of FAS with PLVI may be useful to plan a correct follow-up in patients with breast neoplasms.

Immunohistochemical expression of fatty acid synthase, apoptotic-regulating genes, proliferating factors, and ras protein product in colorectal adenomas, carcinomas, and adjacent nonneoplastic mucosa.

The normal mucosa-adenoma-carcinoma sequence in colon pathology provides an attractive model of tumor progression. The role of tumor suppressor genes, oncogenes, and proliferative markers in tumorogenesis has evolved considerably in the last decade. By immunohistochemistry means, we have studied p53, bcl-2, c-myc, p21-ras, ki67, and fatty acid synthase (a fatty-acid-synthesizing enzyme) in normal, dysplastic, and neoplastic mucosa. The results were correlated with clinicopathological features and overall survival (OS). Formalin-fixed, paraffin-embedded archival material from 100 nonconsecutive adenomas and 100 adenocarcinomas (ADCs), including adjacent-to-tumor nonneoplastic mucosa (ANNM), from patients with a 5-year follow-up period were studied. Negative controls were obtained from colon resections for nonneoplastic disease. Fatty acid synthase was associated with ADC (P = 0.0001). p53 protein was associated with high-grade dysplasia adenoma (AHGD), ADC (P = 0.0001), and pT stage (P = 0.003). bcl-2 was associated with adenomas with low-grade dysplasia (P = 0.009); c-myc was associated with ANNM (P = 0.005) and pT stage (P = 0.006). p21-ras was associated with AHGD (P = 0.0001) and ANNM (P = 0.01). Ki67 was associated with AHGD (P = 0.02) and ADC (P = 0.0001). Univariate analysis on neoplastic tissue revealed histological grade, pT stage, pN stage, p21-ras, and p53 to be significant markers of OS; p21-ras, p53, and c-myc were reliable markers when evaluated on ANNM. Multivariate analysis revealed pT stage, pN stage, and p21-ras to be independent prognosticators of OS on ADC; p21-ras and c-myc staining in the ANNM were correlated with worse survival (OS). We suggest that the evaluation in concert of clinicopathological data and immunohistochemical markers on both normal and abnormal colon tissue provides an attractive model of tumor progression; moreover, it may give important messages about the prediction of survival.

[A case of multifocal inflammatory pseudotumor of the liver]. / Su un caso di pseudotumore infiammatorio multifocale del fegato.

INTRODUCTION: The inflammatory pseudotumor (IPT) of the liver is a tumor-like lesion of unknown etiology and pathogenesis. Non infectious by definition the lesion is considered to be a long-lasting inflammatory process. CASE: In this report we describe a multifocal liver pseudotumor of a 52 year man who underwent a selective hepatectomy for a clinical and radiological suspicion of a liver cell carcinoma. RESULTS: Grossly the masses consisted of rubbery grey-yellowish nodules well-circumscribed from the liver parenchyma. Histologic examination revealed a double shaped cellular population surrounded by a thin rim of collagen fibres. The main population consisted of fibroblasts and histiocytes with no atypias or mitoses, arranged in a storiform or fascicular pattern; the second population consisted of a mixed population of lymphocytes, plasma cells, neutrophils and monocytes. Fibroblasts and histiocytes revealed diffuse positive immunostaining for vimentin and focal immunostaining for cytokeratin and desmin. The histiocytes were also CD68, CD18, CD14 and CD4 positive. CONCLUSIONS: Our case reveals same histological and immunohistochemical features already reported in literature. Primary and metastatic tumors involving the liver need to enter in the differential diagnosis but IPT lacks features of malignancy and the cell population is mixed. Although there is no specific marker for this lesion in cases featuring malignancy immunohistochemistry may be useful for a differential diagnosis: S-100 in cases of neurofibrosarcomas, actin and myosin for rhabdomyosarcomas, cytokeratin for epithelial tumors.

[Terata catydidymus dicephalus: description of a case]. / Terata catydidymus dicephalus: descrizione di un caso.

Conjoined twinning is the result of an abnormal developmental process of "twinning" in which two similar weighted and sized twins are partially conjoined and show a total symmetry independently from the pattern of conjunction. They are classified in three groups: Terata Catydidymus, Terata Anadidyma and Terata Anacatadidyma. Among Terata Catydidymus the dicephalus subtype is a rare abnormality with a severe prognosis compared to other subtypes as: diprosopus, pyophagus and ischiopagus. We report the case of a fetus at the 15th weeks of pregnancy. The external examination revealed severe diffuse somatic malformations consisting of dicephalia with a double neck in conjunction to a single chest, a single abdomen, a double spine conjoined distally near the sacrum, buds of ribs in between the two spines with mid clavicular and scapular fusion following the major axis of the two bones. Arms and legs revealed no abnormalities. Central nervous system structures were normally developed and the two hemispheres seemed completely separated and independent one to the other. We believe that the case described is interesting being Terata Catydidymus a rare phenomenon, being the dicephalus subtype still lesser frequent and its occurrence in males quite exceptional.

Expression of fatty acid synthase (FAS) as a predictor of recurrence in stage I breast carcinoma patients.

BACKGROUND: Fatty acid synthase (FAS) is a molecule found in tumor cells from breast carcinomas of patients whose prognosis is very poor. Recently, this molecule has been identified as the key enzyme in fatty acid biosynthesis. This study was done to test the strength of FAS as a prognostic indicator for disease free survival (DFS) and overall survival (OS). METHODS: Clinical records, histologic features, immunohistochemical expression of cathepsin D and c-erbB-2, and estrogen and progesterone receptor status of 110 Stage I breast carcinoma patients were all associated with FAS by a chi-square test. The patterns of DFS and OS were estimated over a ten-year follow-up period using the Kaplan-Meier method. Univariate and multivariate analysis were evaluated using a log logistic regression model. Multivariate regression analysis was based on the Cox proportional hazard model. To detect FAS, cathepsin D and c-erbB-2 expression as well as estrogen and progesterone receptor status, we used the unlabeled immunoperoxidase technique on formalin fixed, paraffin embedded tissue. RESULTS: FAS was significantly associated with a higher risk of recurrence because it predicted both DFS (P = 0.0001) and OS (P = 0.003) when evaluated as a continuous variable and DFS (P = 0.0001) when evaluated with other prognostic markers. Peritumoral lymphatic vessel invasion was the other most significant independent predictor for DFS (P = 0.001) and OS (P = 0.003). CONCLUSIONS: FAS is a reliable prognostic marker to predict DFS and OS in patients with early breast cancer.

AIDS-related CNS cryptococcosis: radiologic-pathologic correlation.

PURPOSE: This study evaluates the effectiveness of cranial CT and MR in detecting autopsy findings of AIDS-related CNS cryptococcosis. METHODS: Final imaging studies compared with pathology were CT in eight patients (five with contrast) and MR in five patients (all with Gd-DTPA). RESULTS: Neither modality effectively identified cryptococcal meningitis. Punctate hyperintensities were seen in all patients with MR and corresponded pathologically to both perivascular spaces dilated by cryptococcal infection and cryptococcomas. Pathologically, cryptococcomas were more common than dilated perivascular spaces. MR detected more cryptococcomas than did CT, but both modalities underestimated the number of lesions seen at autopsy. Contrast enhancement of cryptococcomas and cryptococcal meningitis was uncommon. CONCLUSIONS: CNS cryptococcosis was more effectively demonstrated by MR than by CT, but both modalities underestimated the pathologic extent of the disease. Cryptococcal lesion contrast enhancement was unusual possibly because of the immunocompromised state of our patients and the unique characteristics of the organism itself.