cyclin-d1 and Keratosis

Morphological diagnosis of cervical intraepithelial neoplastic (CIN) lesions sometimes requires an additional study of molecular markers. Cyclin D1 is a key regulatory protein, which regulates cell cycle progression from G1 to S phase. Disruption of G1/S regulatory mechanisms is basic mechanism of HPV mediated malignant transformation of cervical epithelium. The aim of the research was to study the peculiarities of cyclin D1 protein expression in reproductive and menopausal women with cervical hyperkeratosis. We examined cyclin D1 protein expression in 381 reproductive and 233 menopausal women with cyto-colposcopically detected and histologically proved hyperkeratosis, using immunohistochemical method. Monoclonal ready to use (RTU) antibody against cyclin D1 antigen (Dako) was used. Cyclin D1 positivity in ≤50% of cells considered as low and in ≥50% - as high expression. High expression of cyclin D1 was present in CIN1 of 93,3% reproductive and 66,7% menopausal women, whilst in CINII the high expression was revealed in 53,3% and 43,8% respectively. The weak expression of cyclin D1 was present in only one cases of CINIII, other CINIII cases were all negative. The expression of cyclin D1 protein in cervical intraepithelial neoplastic lesions is not regular, however the overexpression of cyclin D1 is almost always present in CIN1 of reproductive women, in which it might be considered as an additional diagnostic marker.

Topics: Biomarkers, Tumor; Carcinogenesis; Cyclin D1; Female; Humans; Keratosis; Menopause; Reproduction; Uterine Cervical Dysplasia

While cell-cycle markers have been used to differentiate benign vs. malignant lesions and to classify malignant lesions, benign keratoses have not been well studied using such markers. We hypothesized that inflammation or irritation of benign keratoses may be related to a shift in the cell cycle. We compared the immunohistochemical staining patterns of 10 seborrheic keratoses (SKs), 10 inflamed seborrheic keratoses (iSKs), and 10 inverted follicular keratoses (IFKs) using antibodies to p53, bcl-1, and bcl-2. Staining with antibodies to p53 was slightly increased in IFKs compared with iSKs or non-inflamed seborrheic keratoses. Bcl-1 staining was similar in all lesions. A population of bcl-2-positive dendritic cells was seen within the epidermal portion of IFKs. Keratinocyte bcl-2 staining was significantly higher in SKs compared with the other two keratoses. Bcl-2 may be increased in SKs as an anti-apoptotic mechanism.

Topics: Biomarkers; Cell Cycle; Cyclin D1; Darier Disease; Humans; Immunohistochemistry; Inflammation; Keratosis; Keratosis, Seborrheic; Proto-Oncogene Proteins c-bcl-2; Staining and Labeling; Tissue Distribution; Tumor Suppressor Protein p53

The expression of cell-cycle progression molecules cyclin D1 and cyclin E were immunohistochemically examined in a series of 64 squamous cell invasive carcinomas of the larynx, 10 in situ carcinomas, 34 cases of dysplasia, 11 papillomas and 23 cases of keratosis. The results of their expression were compared with two cell-cycle implicated tumor suppressor proteins p53 and pRb as well as with two proliferation associated indices PCNA and Ki-67 in an attempt to elucidate their potential role in the pathogenesis and progression of these lesions. Nuclear staining for cyclin D1 and E (>5% positive cells) was observed in 19% and 39.7% of the laryngeal carcinomas, respectively. Significantly elevated levels of cyclin D1 and E in invasive laryngeal carcinomas compared with in situ carcinomas were revealed (p=0.045 and p=0.0003, respectively). High levels of cyclin D1 and E expression were correlated with increased Ki-67 score (p=0.037 and 0.017 respectively). A significant positive correlation between cyclin D1 and E was also detected in carcinomas (p=0.018). Decreased levels of cyclins D1 and E in the group of in situ carcinomas compared with those of dysplastic cases and papillomas were also observed. In the dysplastic lesions cyclin D1 expression was correlated with pRb expression (p=0.02). In the cases of keratosis cyclins D1 and E expression were correlated with pRb (p=0.002 and p=0.036, respectively), while cyclin D1 was associated with PCNA (p=0.008) and Ki-67 score (p=0.009). The prognostic significance of cyclins D1, E in determining the risk of recurrence and overall survival with both univariate (long-rang test) and multivariate (Cox regression) methods of analysis showed no statistically significant differences. We conclude that the expression of cyclins D1 and E in squamous cell carcinomas of the larynx does not seem to have a prognostic significance. In addition, their expression may be involved in the development of laryngeal lesions, implicated in cell proliferation, with other cell cycle related proteins, probably by different molecular pathways.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma in Situ; Carcinoma, Squamous Cell; Cell Cycle; Cohort Studies; Cyclin D1; Cyclin E; Female; Humans; Immunoenzyme Techniques; Keratosis; Ki-67 Antigen; Laryngeal Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Neoplasms, Glandular and Epithelial; Papilloma; Proliferating Cell Nuclear Antigen; Retinoblastoma Protein; Tumor Suppressor Protein p53