p16 and pRb immunohistochemical expression increases with increasing tumour grade in mammary phyllodes tumours.
OBJECTIVE
Control of cell cycling and proliferation is critical to the development of neoplasia and may play a role in the pathogenesis of phyllodes tumours (PTs). This study aimed to evaluate the immunohistochemical expression of certain proteins from the G(1)/S transition of the cell cycle in a cohort of PTs, to determine their role in tumour pathogenesis and to identify any associations with patient outcome.


RESULTS
Sixty-five PTs (34 benign, 23 borderline and eight malignant) diagnosed at a single institution between 1990 and 2006 were analysed. Immunohistochemistry for p16, pRb, cyclin D1 and Ki67 was performed. Expression of the following markers increased significantly with tumour grade: stromal nuclear and cytoplasmic p16 (P = 0.01 and 0.002, respectively), stromal and epithelial pRb (P = 0.000,000,06 and 0.004, respectively), and stromal and epithelial Ki67 (P = 0.03 and 0.04, respectively). Epithelial pRb scores of 7 (range 0-7) were significantly associated with reduced disease-free survival (DFS) compared with scores of <7 (P = 0.0009). No relationship was found between cyclin D1 expression in either the epithelium or the stroma, and grade or DFS.


CONCLUSIONS
The results suggest that alterations at the G(1)/S transition of the cell cycle play an important role in the progression of PTs.
Karim
Rooshdiya Z
RZ
Department of Anatomical Pathology, Royal Prince Alfred Hospital, Sydney, NSW, Australia. rooshdiya.karim@sswahs.nsw.gov.au
Gerega
Sebastien K
SK
Yang
Y H
YH
Spillane
Andrew
A
Carmalt
Hugh
H
Scolyer
Richard A
RA
Lee
C Soon
CS
D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D019938:Cyclin D1 / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D003557:Phyllodes Tumor / Q000378:metabolism* / Q000473:pathology; D016160:Retinoblastoma Protein / Q000378:metabolism*; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D016160:Retinoblastoma Protein; D019938:Cyclin D1