cyclin-d1 and Carcinosarcoma

Carcinosarcomas are a very rare group of true malignant tumors of the salivary gland. As the name indicates, the tumor is composed of an epithelial and a mesenchymal component, both malignant. We report a case of carcinosarcoma of the submandibular gland in an 86-year-old woman. The epithelial component showed a squamous carcinoma phenotype, whereas the mesenchymal component was morphologically similar to a fibrosarcoma. The epithelial component was strongly positive for CK13, CK14, and AE1/AE, and groups of positive cells were seen for CK19 and vimentin. The whole mesenchymal component was positive for vimentin, negative for cytokeratins, and focal cells were positive for smooth- muscle actin. Both components were strongly positive for P53 and Cyclin D1, and focally positive for MDM2. Rare multinucleated giant cells showed expression of CD68, and focal dendritical cells on carcinomatous nests were positive for S-100. The CK7, CK8, Factor XIIIa, c-erbB-2, P16, CDK-4, Rb1, and E2F-1 were not detected in these 2 groups of malignant cell populations.

Topics: Aged, 80 and over; Carcinosarcoma; Cyclin D1; Female; Humans; Immunoenzyme Techniques; Keratins; Submandibular Gland Neoplasms; Tumor Suppressor Protein p53; Vimentin

Carcinosarcoma of the tongue is a rare malignancy and its molecular aspect is unclear. A case of carcinosarcoma of the tongue in a 51-year-old man is presented. A polypoid tumor of the tongue, measuring 12 x 12 x 6 mm, was resected. Histologically, the tumor was composed of a squamous cell carcinoma and a spindle cell sarcomatous component. We previously showed that one cell-cycle regulator, the cyclin D1 gene, was frequently amplified in esophageal carcinosarcoma, which shows the same morphologic features as carcinosarcoma of the tongue. In this case, we examined whether the cyclin D1 gene is amplified in carcinosarcoma of the tongue as well. Fluorescence in situ hybridization analysis revealed that the cyclin D1 gene was amplified in both components of carcinosarcoma of the tongue. The cyclin D1 protein was also detected by immunostaining in both components. Our results suggest that the amplification of cyclin D1 gene plays a role in the molecular pathogenesis of carcinosarcoma of the tongue, at least in some cases.

Topics: Carcinosarcoma; Cyclin D1; Gene Amplification; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Male; Middle Aged; Tongue Neoplasms

The purpose of the present study was to define the overexpression of cyclin D1 in superficial and advanced esophageal carcinomas and to investigate whether the expression of this molecule indicates a poor prognosis. This study included 41 patients with superficial esophageal carcinomas (Tis and T1) and 48 patients with advanced esophageal carcinomas (T2, T3, and T4). The expression of cyclin D1 in surgically resected specimens was evaluated immunohistochemically with a monoclonal antibody. Positive immunoreactivity was found in 31 of 89 cases (35%). Overexpression of cyclin D1 did not correlate with TNM classification or histologic type. Of the 48 patients with advanced esophageal carcinomas, 32 patients with cyclin D1-negative tumors survived longer than did 16 patients with cyclin D1-positive tumors (P = 0.0017). In contrast, we observed no survival difference between patients with cyclin D1-positive and -negative superficial esophageal carcinoma. These results suggest that cyclin D1 indicates a poor prognosis in cases of advanced esophageal carcinoma but not in cases of superficial esophageal carcinoma.

Topics: Biomarkers, Tumor; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Carcinosarcoma; Cyclin D1; Esophageal Neoplasms; Esophagus; Female; Humans; Immunoenzyme Techniques; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis

We studied cyclin D1 gene amplification in four esophageal carcinosarcomas using the differential polymerase chain reaction. Three cases showed amplification in the sarcomatous components, and one of these also showed amplification in the carcinomatous component. No amplification was detected in the other case. We also examined p53 expression in these four tumors by immunostaining. Both components of all four cases showed diffuse overexpression of p53 protein in the nuclei. Our results showed that the cyclin D1 gene is frequently amplified in esophageal carcinosarcoma, especially in the sarcomatous component. Two cases showed amplification only in the sarcomatous component, suggesting that amplification may have a role in the pathogenesis of that component of this malignancy. The diffuse overexpression of p53 observed in both components suggests that such overexpression, which could be the result of somatic mutation, might be an early event in the pathogenesis of esophageal carcinosarcoma.

Topics: Blotting, Southern; Carcinosarcoma; Cyclin D1; DNA Primers; DNA, Neoplasm; Esophageal Neoplasms; Gene Amplification; HeLa Cells; Humans; Immunoenzyme Techniques; Polymerase Chain Reaction; Receptors, Dopamine D2; Tumor Suppressor Protein p53

Cyclin D1 (CD1) gene amplification is frequently observed in esophageal carcinosarcoma by differential polymerase chain reaction (DPCR). In this study, fluorescence in situ hybridization (FISH) was performed to show more direct evidence of CD1 gene amplification in patients with esophageal carcinosarcoma. FISH results were also compared with DPCR results studied previously. FISH analysis revealed CD1 gene amplification in all four patients with esophageal carcinosarcoma. CD1 gene amplification occurred with a high incidence in both components of esophageal carcinosarcoma, suggesting that CD1 gene amplification could have an important role in malignant transformation processes of esophageal carcinosarcoma. The results of the current study also suggest that FISH is a more sensitive method than DPCR. Because inactivation of p16 gene (which is a putative tumor suppressor gene) is thought to have similar oncogenic effects with CD1 gene amplification, DPCR was used to examine whether p16 homozygous deletion occurs in esophageal carcinosarcoma. These results suggest that homozygous deletion of the p16 gene occurs less frequently than CD1 gene amplification in esophageal carcinosarcoma. It does not seem to be an alternative event to CD1 gene amplification, though the number of studied cases was small.

Topics: Aged; Aged, 80 and over; Carcinosarcoma; Cyclin D1; DNA Primers; Esophageal Neoplasms; Gene Amplification; Gene Deletion; Genes, p16; Homozygote; Humans; In Situ Hybridization, Fluorescence; Male; Middle Aged; Molecular Sequence Data; Polymerase Chain Reaction