|
In addition, p27KIP1 has been postulated to promote apoptosis, play a role in terminal differentiation of some tissues, and mediate chemosensitivity in solid tumors. From the list of established and putative functions of p27KIP1, it is not hard to fathom why abrogating p27KIP1 function results in uninhibited cell proliferation and tumorigenesis. Several recent lines of evidence suggest that decreased p27KIP1 expression in tumors is associated with a more aggressive tumor phenotype such as poor histologic grade, presence of lymphovascular invasion and higher growth fraction. p27KIP1 status is also an independent prognostic factor, and loss of p27KIP1 expression is associated with tumor progression, lymph node metastasis, early relapse, and reduced overall survival. These findings have been validated on a host of cancers occurring at various anatomic sites such as breast, colon, esophagus, stomach, lung, and prostate, and virtually all studies were performed using immunohistochemistry for determining p27KIP1 expression. Assessment of p27KIP1 status in solid tumors is thus an useful adjunct to more conventional markers for predicting prognosis.
Veripath OncoDiagnostics offers p27KIP as part of the standard colorectal, esophagus, and stomach cancer panels, but it can also be ordered individually. Currently, we are using an automated image analysis system to quantitatively score percentage positivity and intensity grade for p27KIP finally reflected in a histoscore on each evaluation. For more information contact Dr Raheela Ashfaq at the OncodDiagnostic Laboratory at 214.645.7053 or Raheela.Ashfaq@UTSouthwestern.edu.
Selected references:
1. Catzavelos C et al. Decreased levels of the cell-cycle inhibitor p27KIP1 protein: prognostic implications in primary breast cancer. Nat Med 3:227; 1997
2. Esposito V et al. Prognostic role of the cyclin-dependent kinase inhibitor p27KIP1 in non-small cell lung cancer. Cancer Res 57:3381; 1997
3. Lloyd RV et al. p27KIP1 : a multifunctional cyclin-dependent kinase inhibitor with prognostic significance in human cancers. Am J Pathol 154:313; 1999.
4. Tsihilas J et al. Loss of cyclin-dependent kinase inhibitor p27KIP1 is a novel prognostic factor in localized human prostate adenocarcinoma. Cancer Res 58:542; 1998 |
