Age, smoking, N3 disease, T4 disease, and a negative p16 status were associated with the development of distant metastases in patients with squamous cell cancers of the oropharynx treated definitively with concurrent chemoradiation.
Differentiation degree, clinical stage, metastases of nearby lymph nodes and distant metastasss were negatively related with p16 gene expression (p less than 0.05).
HPV tumor status testing may be performed by surrogate marker p16 immunohistochemistry either on the primary tumor or from cervical nodal metastases only if an oropharyngeal primary tumor is present.
A primary HNcSCC should be considered in p16 positive neck node metastases in regions with high prevalence of HNcSCC. p16 expression is not associated with improved survival in HNcSCC.
In contrast, in basal-like tumours, c-MYC showed positive association with Cyclin E (P=0.003) and p16 (P=0.042) expression only. c-MYC was an independent predictor of a shorter distant metastases-free survival in luminal A LN+ tumours treated with endocrine therapy (ET; P=0.013).
We immunohistochemically analyzed p16 expression in surgically resected aggressive cutaneous head and neck SCC primaries and their nodal metastases from 24 patients to determine the potential overlap of p16 expression outside of the oropharynx.
The alterations of p16 gene may play a major role in malignancy and development and metastases of buccal carcinoma and may be an excellent marker of aggressive clinical behavior.
A positive HPV-specific polymerase chain reaction finding correlated significantly with p16 overexpression in both primary tumours and their metastases (P<0.0001 for both).
To better understand the roles of p16 in pancreatic tumorigenesis, we created a conditional p16 knockout mouse line (p16flox/flox), in which p16 is specifically disrupted in a tissue-specific manner without affecting p19/ARF expression. p16flox/flox; LSL-KrasG12D; Pdx1-Cre mice developed the full spectrum of pancreatic intraepithelial neoplasia (mPanIN) lesions, pancreatic ductal adenocarcinoma (PDA), and metastases were observed in all the mice.
Correspondingly, nuclear p16 expression was found immunohistochemically in five (10.9%, mean IRS = 0.5) HCCs, 23 (92%; mean IRS = 4.9) metastases and only occasionally in hepatocytes of non-lesional liver tissues (mean IRS = 1.2).
In addition, the expression of p16 was highly predictive for reduction of the survival in patients who were affected by metastases or recurrence (P = .041).
The genetic comparison of 15 primary ECs and their paired metastases revealed that in most of the cases the deleted region of p16 gene remains the same or becomes larger during the progression from primary tumor to its corresponding metastases.
P16 expression also correlated with site of tumor origin: 13 of 19 oropharyngeal metastases were p16 positive, whereas only 1 of 46 non-oropharyngeal metastases was p16 positive (68% versus 2%; P < 0.0001).
Diffuse (>75% positive tumor cells) moderate to strong p16 expression is a sensitive (100%) and specific (97%) marker for identifying HPV-related endocervical adenocarcinomas metastatic to the ovary among the primary ovarian tumors and metastatic adenocarcinomas from other sites that are in the differential diagnosis of ovarian tumors having mucinous and/or endometrioid/endometrioidlike differentiation. p16 is useful as part of a panel of immunohistochemical markers for distinguishing primary ovarian tumors from metastases and, when diffusely positive, can suggest the cervix as a potential primary site for metastatic adenocarcinomas of unknown origin.
A much higher proportion of methylated p16 was detected in GCs with metastases (local or distant) than without metastases (14.76 vs 2.61%; t-test P=0.014).
Complete loss of MTAP and p16 was seen in 4 of 25 (16%) patients with Barrett's esophagus, 4 of 18 (22%) with low-grade dysplasia, 5 of 39 (13%) with high-grade dysplasia, 17 of 78 (22%) with invasive adenocarcinoma, and 8 of 36 (22%) of metastases.
To investigate whether alterations in Cyclin D1, p14, CDK4 and Rb are associated with tumour cell proliferation, tumour progression and patient survival in malignant melanoma, we examined 202 vertical growth phase tumours and 68 corresponding metastases for expression of Cyclin D1, p14, CDK4 and Rb, and compared the results with Ki-67 expression, p16 and p53 expression, clinico-pathological variables, and survival data.
The results revealed that nuclear expression of beta-catenin, p16 and c-myc was quantitatively increased from normal mucosa to premalignant adenoma, primary carcinoma and lymph node metastatic carcinoma; the frequency of nuclear overexpression of beta-catenin and p16 in lymph node metastases was significantly higher than that in distant metastases (p < 0.05).
This paper reviews the current literature on p16 expression in melanoma and pancreatic cancer, explores factors that place patients with these cancers in categories of high risk for metastases or recurrence, and addresses whether aberrant gene expressions should influence awareness of and current recommendations for the management of these aggressive cancers.
The status of the P16 gene was investigated by Southern blot, polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP), and DNA sequencing analyses in 30 primary resected non-small cell lung carcinomas (NSCLCs) with metastatic involvement of thoracic lymph nodes and 33 NSCLCs without node metastases.