cyclin-d1 and Breast-Diseases

To study the value of immunocytochemical study for cyclin D1, c-erbB-2, Ki-67, p21(CIP1/WAF1) and 34betaE12 in fine needle aspiration cytology (FNAC) diagnosis of mammary lesions.. One hundred and thirty-five cases of breast diseases, all with FNAC performed and follow-up histologic correlation available, were enrolled into the study. These included 43 cases of benign non-proliferative diseases, 45 cases of benign proliferative diseases and 47 cases of mammary carcinoma. Immunostaining for cyclin D1, c-erbB-2, Ki-67, p21(CIP1/WAF1) and 34betaE12 was carried out on FNAC smears and paraffin sections of the corresponding biopsy specimens. The statistical significance was analyzed using SPSS11.5 software.. No statistically significant difference was observed in the expression of cyclin D1, c-erbB-2, Ki-67, p21(CIP1/WAF1) and 34betaE12 within the groups of benign non-proliferative and benign proliferative breast diseases. On the other hand, a significant difference in immunostaining results was found between benign breast lesions and mammary carcinoma (P < 0.001). A panel of cyclin D1, 34betaE12 and c-erbB-2 immunostaining is highly sensitive and specific in confirming the diagnosis of mammary carcinoma in FNAC samples. A positive reaction for cyclin D1 and c-erbB-2, when coupled with a negative reaction for 34betaE12, showed to be the most reliable supportive evidence for the malignant cytologic diagnosis. When taking the results of either cyclin D1 or 34betaE12 immunostaining into consideration, the sensitivity and specificity for diagnosing carcinoma was 95.7% and 94.3% respectively. On the other hand, when any of the three immunostains suggested carcinoma, the diagnostic sensitivity and specificity became 97.9% and 92.0% respectively. If the immunostaining results of any two of the three markers suggested carcinoma, the diagnostic sensitivity and specificity became 72.3% and 100% respectively. Within the carcinoma group, the degree of expression of cyclin D1, p21(CIP1/WAF1) and 34betaE12 showed little difference amongst different cytologic grades (according to Robinson cytologic grading system). There were however differences in expression of c-erbB-2 and Ki-67. Highest expression rate was observed in grade 3 carcinoma, while lowest expression rate was observed in grade 1 carcinoma (only in 40.0% and 33.3% of cases respectively). Whenever either cyclin D1 positivity or 34betaE12 negativity was demonstrated, the diagnostic accuracy for grade 1 and grade 2 carcinoma was 93.3% and 96.2 % respectively.. Immunocytochemical study using a panel of antibodies for cyclin D1, c-erbB-2, and 34betaE12 has significant diagnostic value in distinguishing between benign breast diseases and mammary carcinoma in FNAC samples. Cyclin D1 and 34betaE12 are especially useful in confirming the cytologic diagnosis of low-grade cancer.

Topics: Biopsy, Fine-Needle; Breast; Breast Diseases; Breast Neoplasms; Carcinoma; Cyclin D1; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Receptor, ErbB-2

Cyclin D1 plays a critical role in regulating cell-cycle progression. Gene amplification and protein overexpression of cyclin D1 have been detected in breast cancer but little is known concerning whether these changes occur in normal breast tissue and in breast lesions associated with increased risk of development of invasive breast cancer. We looked for cyclin D1 gene amplification and protein overexpression in 30 cases of benign breast disease (16 epithelial hyperplasias without atypia and 14 atypical ductal hyperplasias) and 18 ductal carcinomas in situ by use of differential PCR and immunohistochemical staining. We compared the resulting frequencies to those in 15 cases of normal breast tissue and 17 invasive ductal carcinomas. We found cyclin D1 gene amplification in 15% of those with normal breast tissue, 19% of those with epithelial hyperplasia without atypia, 27% of those with atypical ductal hyperplasia, 35% of those with ductal carcinoma in situ, and 25% of those with invasive ductal carcinoma; corresponding figures for protein overexpression were 13, 13, 57, 50, and 64%. These results suggest that cyclin D1 amplification and protein overexpression can occur before histologic alterations are seen but that the frequencies of these changes are higher in histologic lesions with cellular atypia (atypical hyperplasia and ductal carcinoma in situ), reaching frequencies similar to those observed in invasive carcinoma.

Topics: Breast; Breast Diseases; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal, Breast; Cyclin D1; DNA, Neoplasm; Gene Amplification; Gene Expression; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Tumor Cells, Cultured

Patients with benign breast biopsies that exhibit atypical epithelial proliferation or fibroadenoma may be at increased risk for invasive breast cancer. We hypothesized that molecular markers might also be useful to evaluate the malignant potential of nonneoplastic breast tissue.. Study subjects belonged to a cohort of 6,805 women who underwent biopsy for nonmalignant breast disease at the Mayo Clinic and Rochester-affiliated hospitals between 1967 and 1981. As part of a nested case-control study that compared subjects who developed invasive breast cancer with those who did not, we analyzed a sample of 60 benign breast biopsies for the following markers: HER-2/neu and p53 over-expression by immunohistochemistry, HER-2/neu and PRAD-1 amplification using differential polymerase chain reaction (PCR), and p53 mutation using single-strand conformation analysis (SSCA) and direct DNA sequencing by asymmetric PCR.. None of 60 biopsies showed amplification of HER-2/neu or PRAD-1. Five samples exhibited low-level immunoreactivity to the HER-2/neu protein product. Fourteen samples exhibited focal or diffuse immunoreactivity to the p53 protein. Point mutations in the p53 gene were found in five samples: three of these samples exhibited mutations that altered the amino acid sequence. Only two of five samples with p53 mutation exhibited p53 overexpression. Histologic diagnoses on three samples with nonconservative p53 mutation were, respectively, nonproliferative fibrocystic change, papillomatous hyperplasia, and fibroadenoma.. The clinical significance of p53 mutation, p53 overexpression, and low-level HER-2/neu expression in benign breast tissue remains to be determined. Further research will be necessary to evaluate whether these markers could serve as useful adjuncts to histology in evaluation of the malignant potential of benign breast tissue.

Topics: Base Sequence; Biopsy; Breast Diseases; Breast Neoplasms; Case-Control Studies; Cyclin D1; Cyclins; DNA Mutational Analysis; Female; Fibroadenoma; Fibrocystic Breast Disease; Gene Amplification; Genes, p53; Humans; Hyperplasia; Immunohistochemistry; Molecular Sequence Data; Oncogene Proteins; Point Mutation; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Receptor, ErbB-2; Tumor Suppressor Protein p53