cyclin-d1 and Histiocytoma--Benign-Fibrous

Dermatofibrosarcoma protuberans (DFSP) and histiocytofibroma (HF) are two rare fibrohistiocytic tumors, with some overlapping pathologic features. Immunohistochemistry is very useful in these cases. CD34 is a commonly used marker. However, the increasing cases of CD34 negative DFSP make it pressing to test other immunohistochemical markers that could help in the differential diagnosis. DFSP is known to harbor COL1A1-PDGFB rearrangement. Tumors in the differential diagnosis of DFSP usually lack this molecular signature. Recent studies suggested the interaction of PDGFB and PDGF receptor b with various signaling pathways, including the Akt-mTOR pathway. Cyclin D1, one of the oncoproteins activated in this pathway, may represent a promising useful biomarker in the differential diagnosis. On the other hand, CD10 expression in specialized mesenchymal skin cells, and especially in fibrohistiocytic skin tumors has been reported, which raises the interest of using this biomarker in HF and DFSP. In this study, we aimed to compare the expression of CD10 and cyclin D1 in 15 cases of DFSP and 15 cases of HF and discuss their potential contribution in the differential diagnosis.

Topics: Adolescent; Adult; Biomarkers, Tumor; Cyclin D1; Dermatofibrosarcoma; Female; Histiocytoma, Benign Fibrous; Humans; Male; Middle Aged; Neprilysin; Retrospective Studies; Skin Neoplasms; Young Adult

Topics: Anaplastic Lymphoma Kinase; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Cyclin D1; Diagnosis, Differential; Epithelioid Cells; Female; Foot; Granular Cell Tumor; Histiocytoma, Benign Fibrous; Humans; Immunohistochemistry; Middle Aged; Skin Neoplasms

Topics: Aged; Cyclin D1; Dermis; Diagnosis, Differential; Female; Fibrosarcoma; Follow-Up Studies; Forearm; Histiocytoma, Benign Fibrous; Humans; Prognosis; Soft Tissue Neoplasms

Flavopiridol is the potent inhibitor of cdks sharing its function with endogenous cdk inhibitors, and causes arrest at both the G1 and G2 phases of the cell cycle resulting in apoptosis in various tumor cell lines. Cyclin-dependent kinase inhibitor p16INK4a induces cell cycle arrest in G1 or G2 or both, and is inactivated in many malignant tumors. In this study, we focused on the effects of flavopiridol on chemically-induced rat lung adenocarcinoma, osteosarcoma and malignant fibrous histiocytoma (MFH) cell lines showing different pattern of p16INK4a status. The data demonstrated that flavopiridol inhibited cellular growth in a dose- and time-dependent manner, inducing apoptosis within 24 h in all cell lines at a concentration of 300 nM. The growth inhibition rate was the greatest for lung adenocarcinoma cells, lacking p16INK4a expression associated with methylation-mediated gene silencing; 83% at a concentration of 300 nM for 72-h treatment; while the growth of osteosarcoma and MFH cells, both expressing p16INK4a, were inhibited at similar levels; 54-61% for osteosarcoma and 61-64% for MFH cell lines. Then, we further investigated the influence of p16INK4a induction upon the effect of flavopiridol in p16INK4a-deficient lung adenocarcinoma cells. 5-aza 2'-deoxycytidine (5-Aza-CdR) induced p16INK4a expression and inhibited cellular growth in lung adenocarcinoma at a similar level to that with flavopiridol treatment. After the induction of p16INK4a expression by 5-Aza-CdR, the growth inhibition rates of flavopiridol in the p16INK4a-induced lung adenocarcinoma cells could not achieve comparable inhibition to that in the p16INK4a-deficient cells; the efficacy was reduced compared to original p16INK4a-deficient cells at each concentration of 50, 100 and 500 nM for 72-h treatment. These data indicate that flavopiridol shows cell type specific inhibition and possibly acts in a more compensatory manner for endogenous p16INK4a function in tumor cells having the aberrations of p16INK4a gene.

Topics: Adenocarcinoma; Animals; Apoptosis; Bone Neoplasms; Cell Division; Cell Line, Tumor; Cyclin D1; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase Inhibitor p16; Cyclin-Dependent Kinases; DNA Methylation; Flavonoids; Gene Expression Regulation, Neoplastic; Histiocytoma, Benign Fibrous; Lung Neoplasms; Osteosarcoma; Piperidines; Promoter Regions, Genetic; Proto-Oncogene Proteins; Rats; RNA, Messenger

Overexpression of cyclin D1 and p53 protein has been reported in many types of malignant tumors.. We investigated whether cyclin D1 was detected immunohistochemically in various types of malignant tumors of the skin, comparable with p53 protein.. Immunohistochemical staining of cyclin D1 and p53 protein was applied to squamous cell carcinoma, malignant melanoma and malignant fibrous histiocytoma and various kinds of benign skin tumors.. Cyclin D1 was positive only in malignant tumors at the same incidence as p53 protein.. Cyclin D1 immunohistochemical staining may be a malignant marker for various skin tumors.

Topics: Biomarkers; Biopsy, Needle; Carcinoma, Squamous Cell; Cyclin D1; Cyclins; Histiocytoma, Benign Fibrous; Humans; Immunohistochemistry; Melanoma; Oncogene Proteins; Sensitivity and Specificity; Skin Neoplasms; Tumor Suppressor Protein p53