Cyclin D1 (PRAD1) protein expression in breast cancer: approximately one-third of infiltrating mammary carcinomas show overexpression of the cyclin D1 oncogene.
Amplification of chromosome 11q13 has been observed in 10-20% of breast carcinomas and numerous other tumors, including squamous cell carcinomas of the head, neck, and esophagus; transitional cell carcinomas of the urinary bladder; and epithelial ovarian tumors. Cyclin D1/PRAD1 is a likely "driver" gene for this amplicon because of its role in cell cycle control and because it has been specifically implicated as an oncogene in parathyroid adenomas and B-cell lymphomas with 11q13 translocation breakpoints. We examined cyclin D1 protein expression in 48 consecutive cases of infiltrating mammary carcinoma using an affinity-purified polyclonal antisera to cyclin D1 and a microwave/citrate buffer antigen retrieval system. Staining data were correlated with clinicopathological features, protein detection by immunoblots, and 11q13 DNA amplification. Definite nuclear staining was seen in 17/48 (35%) tumors (16 infiltrating ductal carcinomas, predominantly grade 2/3, and one infiltrating lobular carcinoma). There was no nuclear staining of normal breast epithelium, fat cells, or admixed lymphocytes. Tumors with overexpression of cyclin D1 were estrogen receptor-positive (P < .005) and usually progesterone receptor-positive (P < .005) but otherwise were similar to other negative cases in the study group. Correlation between Western blot and immunostaining data was excellent (P < .01). Five of the 22 cases studied showed 11q13 DNA amplification as well as increased levels of cyclin D1 protein by Western blot and immunostaining. Four cases with increased cyclin D1 protein by both western blots and immunohistochemistry did not have detectable 11q13 amplification. Nuclear cyclin D1 protein can be detected in approximately one-third of infiltrating breast carcinomas using an immunohistochemical technique on formalin-fixed, paraffin-embedded tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
Zukerberg
L R
LR
Department of Pathology, Massachusetts General Hospital, Boston, USA.
Yang
W I
WI
Gadd
M
M
Thor
A D
AD
Koerner
F C
FC
Schmidt
E V
EV
Arnold
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019938:Cyclin D1; D016213:Cyclins / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015513:Oncogene Proteins / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012189:Retrospective Studies
D016213:Cyclins; D004273:DNA, Neoplasm; D015513:Oncogene Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D019938:Cyclin D1