p27 and salivary cancer.
This study examined p27 expression in a cohort of salivary malignancies (n = 74) for a prolonged period (20 years). Reduction of p27 expression was found to be a most powerful predictor for poor survival and more so when the tumor concurrently expressed high levels of p53, TUNEL and heparanase markers, dramatically dropping the patient survival probability to 0! While no patient whose tumor-staining profile included: p27 > 50%, p53 = 0, TUNEL = 0 and heparanase = 0, died of the disease during the 20-year follow up, the median of survival of the group with p27 <or= 50%, p53 > 0, TUNEL > 0 and heparanase > 0 was only 39 months. The survival probabilities of these two groups at 5 years were 100 and 50%, respectively, and at 20 years they were 100 and 0%, respectively (P = 0.05). Significant p27 reduction also resulted in significantly larger tumor size (T value), higher spread of neck metastasis and extra capsular spread and in more advanced disease (higher stage). Significant correlation rates were found between age and poor survival, age and reduced p27 expression, and reduced p27 expression and other general co-existing malignancies, indicating p27 reduction as part of a general phenomenon-age related mutagenesis. Significantly more extensive therapy applied to patients with salivary reduced-p27 tumors could not prevent the rise in mortality rate, questioning the justification for extensive therapy which is naturally accompanied by higher morbidity. Additional therapeutic tools for fighting salivary cancer, possibly based on the new understanding of the p27, p53, TUNEL and heparanase carcinogenic network, are necessary.
Ben-Izhak
Ofer
O
Department of Pathology, Rambam Medical Center, Haifa, Israel.
Akrish
Sharon
S
Gan
Shlomit
S
Nagler
Rafael M
RM
D000368:Aged; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012468:Salivary Gland Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D012469:Salivary Glands / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000099175:Heparanase
D050760:Cyclin-Dependent Kinase Inhibitor p27; D005966:Glucuronidase; D016159:Tumor Suppressor Protein p53; D000099175:Heparanase; C495901:TP53 protein, human