Five variants were previously reported to confer risk of various malignant or benign tumors (rs78378222 in TP53, rs10069690 in TERT, rs1800057 and rs1801516 in ATM, and rs7907606 at OBFC1) and four signals are located at established risk loci for hormone-related traits (endometriosis and breast cancer) at 1q36.12 (CDC42/WNT4), 2p25.1 (GREB1), 20p12.3 (MCM8), and 6q26.2 (SYNE1/ESR1).
p14 absent expression was associated with malignant tumors (60 % positive) (p = 0.000), while 93 % and 94 % of benign and borderline tumors, respectively, were positive. p16 was positive in 94.6 % of carcinomas, 75 % of borderline and 45.7 % of benign tumors (p = 0.000). p53 negative staining was associated with benign tumors (2.9 % positive) (p = 0.016) but no difference was observed between borderline (16.7 %) and malignant tumors (29.7 %) (p = 0.560).
The identification of LOH involving TP53 and RB1 loci is a novel finding in benign cutaneous neurofibromas possibly demonstrating an alternative underlying molecular mechanism associated with the development of these benign tumors from this cohort of patients.
Whereas immunostaining for p53 has been suggested as an adjunct tool to differentiate benign spiradenoma, cylindroma, and spiradenocylindroma from their malignant counterparts, its utility is limited by its heterogeneous pattern of expression, especially the sometimes lack of staining in clearly malignant areas and the occurrence of focal, weak positivity in the benign residua or in unequivocally benign neoplasms.
Thus, p53 effectively prevented the conversion of small benign tumors to malignant and metastatic melanoma. p53 activation in cultured primary melanocyte and melanoma cell lines using Nutlin-3, a specific Mdm2 antagonist, supported these findings.
Strong overexpression of p53 was detected in 3 cases with malignant and none with benign tumors (p >0.05); and strong overexpression of nm23 was detected in 5 cases with malignant and 2 with benign tumors (p >0.05).
Recent evidence indicates that some mutations in p53 arise as the cancer progresses from a benign tumor to a metastatic tumor and that these mutations in p53 actively contribute to the process of cancer progression.
Mdm2 amplification in benign tumors suggests that it is not sufficient for p53 inactivation in cancer, implying that other defects in the p53 pathway are required for malignancy.
In malignant tumours, K-ras mutation, telomerase activity, and p53 overexpression were detectable in 76, 91, and 46%, respectively, while in benign tumours, these alterations were detectable in 38, 0, and 0%, respectively.
The pooled prevalence estimate for p53 overexpression among epithelial ovarian carcinomas was 51% (95% confidence intervals [95% CI], 50-53%) compared with 17% (95% CI, 15-20%) among LMP tumors and 7% (95% CI, 5-10%) among benign tumors. p53 mutation prevalence estimates were 45% (95% CI, 42-47%), 5% (95% CI, 2-9%), and 1% (95% CI, 0-5%), respectively, for invasive, LMP, and benign tumors.
The role of P53 mutations in the program of carcinogenic genetic alterations differs among tumor sites ranging from the earliest mutations that can be detected in premalignant cells to mutations that trigger malignant transformation of a benign neoplasm.
To explore p53 mutations in benign tumours, we have screened 70 colorectal adenomas for allelic loss at, and point mutations in, TP53 by analysis of selected microdissected cell populations.
TP53 status was analyzed by yeast functional assay and DNA sequencing in 12 cases of ameloblastoma which were diagnosed histologically and represented the clinical features of a benign tumor.
Nevertheless, patients with carcinomas showed an overexpression (preferentially cytoplasmic) of p53 protein compared with patients with benign tumours (p<0.05).
On the contrary, strong protein expression of p53 was found in 54% (25/46) of the malignant epithelial tumors examined but similar expression of p53 was not observed in borderline and benign tumors and normal ovarian surface epithelium.
A series of 219 salivary gland tumours (103 carcinomas and 116 benign tumours) were analysed for p53 protein expression using immunohistochemistry, and for mutations in p53 gene using non-radioactive single strand conformation polymorphism (SSCP). p53 expression was present in 36% (42/116) of the benign tumours and in 54% (56/103) of the carcinomas.
On the other hand, the p53 mutation frequency was higher in patients with premalignant tumors or nonmelanocytic skin cancer than in patients with only benign tumors.