80% of primary invasive vulvar SCC were HPV-negative carcinomas with a high frequency of disruptive mutations and "hot spot" TP53 gene mutations, which have been linked to chemo- and radioresistance.
Carcinomas with polymerase E (POLE) exonuclease domain hotspot mutations are highly prognostically favourable; those with copy-number alterations and TP53 mutations are highly aggressive; and microsatellite unstable and 'copy-number low' endometrioid carcinomas are associated with intermediate prognoses.
Carcinomas with POLE domain hotspot mutations are highly prognostically favorable; those with copy number alterations and TP53 mutations are highly aggressive; and microsatellite unstable and "copy number low" endometrioid are associated with intermediate prognoses.
TP53 mutations were not detected in any serous borderline tumors (n = 30) or low-grade serous carcinomas (n = 43) but were found in 73% of high-grade serous carcinomas (n = 18).
TP53 mutations were found in 17 (43.6%) of vulvar cancers, 18 (46.2%) tumors were HPV associated, and 8 (20.5%) carcinomas showed no relation to HPV infection or TP53 mutations.
TP53 mutation (and associated p53 protein overexpression) is probably a negative prognostic marker in endometrial cancers, but its relevance in the rarer histologic subtypes, including clear cell carcinomas, has not been delineated.
TP53 mutations were associated with high-grade carcinomas (p=0.014), advanced FIGO stage (p=0.001), intraoperative residual disease >1cm (p=0.004), as well as poor overall survival (p=0.002).
TP53 mutations are the single most commonly identified mutations in aggressive sporadic high-grade serous carcinomas, affecting essentially 100% of such tumours.
TP53 mutation occurred more frequently in carcinomas than borderline tumors (56.8 % and 11.5 %, respectively), and combined IHC and mutation data suggest alterations occur in approximately 68 % of MC and as many as 20 % of MBOT.
TP53 mutations, previously thought to be restricted to less differentiated carcinomas, were also detected in papillary and follicular carcinoma and found to carry a guarded prognosis.
A P53 mutation in the main tumor was evident in none (0%) of seven stage I or II carcinomas and in nine (38%) of 24 stage III or IV cases, whereas a Ki-ras codon 12 point mutation was present in four (67%) of six stage I or II cases and in 14 (61%) of 23 stage III or IV cases.
A P53 independent pathway seems to be implicated in Waf-1, Bax and Bcl-2 expression with an inversion of the Bax/Bcl-2 ratio restricted to invasive carcinomas.
A better understanding of the prognostic role of TERTp mutation (together with additional ones like BRAF, RAS, PIK3CA, AKT1, or TP53) and the clarification of their putative role in fine-needle aspiration biopsies are likely to allow, in the future, an early refinement of the stratification risk in patients with well-differentiated carcinomas.
A cytotoxic T lymphocyte (CTL) clone generated in vitro from the peripheral blood of a healthy HLA-A2-positive individual against a synthetic p53 protein-derived wild-type peptide (L9V) was shown to kill squamous carcinoma cell lines derived from two head and neck carcinomas, which expressed mutant p53 genes, in a L9V/HLA-A2 specific and restricted fashion.