Detailed correlative analyses of individual patient samples revealed a significantly greater proportion of SCC in TMA set 1 with higher PI3Kβ and lower PTEN expression when compared with adenocarcinoma.
We identified that prostatic intraepithelial neoplasia (PIN) lesions induced by PTEN loss of function (PTEN(LOF)) progress to invasive adenocarcinoma following paracrine expression of either cytokine.
Further evaluations indicated that phospho-Stat3, phospho-Akt, phospho-nuclear factor κB, cyclin D1, and Ki67 were upregulated in adenocarcinomas from ARR(2)Pb.Stat3C x PTEN(+/-) mice.
The PTEN mutation rate was 83% (25 of 30) in endometrioid endometrial adenocarcinomas and 55% (16 of 29) in precancers, and the difference in number of mutations was statistically significant (two-sided P =.025).
The purpose of this study was to determine whether PTEN mutations also are present in endometrial hyperplasias, which are premalignant precursors of invasive endometrial adenocarcinomas.
In a subgroup of non-smokers with adenocarcinoma, EGFR was the most frequently altered gene, with a mutation rate of 49.8%, followed by EML4-ALK (9.3%), PTEN (9.1%), PIK3CA (5.2%), c-Met (4.8%), KRAS (4.5%), STK11 (2.7%), and BRAF (1.9%).
In 35% of adenocarcinomas we found some type of EGFR-PTEN alteration, with a tendency to be associated with advanced-stage prostate adenocarcinomas (P=0.04).
Tissue microarray analysis using interphase FISH indicated that hemizygous PTEN losses were present in 42/107 (39%) of prostatic adenocarcinomas, with a homozygous PTEN deletion observed in 5/107 (5%) tumours.
Thus, ERG has a distinct role in prostate cancer progression and cooperates with PTEN haploinsufficiency to promote progression of HGPIN to invasive adenocarcinoma.
Chromosomal imbalances, loss of heterozygosity, and immunohistochemical expression of TP53, RB1, and PTEN in intraductal cancer, intraepithelial neoplasia, and invasive adenocarcinoma of the prostate.
The current observations suggest that PTEN mutation is frequently detected in HPV-negative adenocarcinomas of the cervix and the most prevalent occurrence of PTEN mutation in endometrioid subtype is keeping with endometrial and ovarian carcinomas.
Accordingly, PTEN-deficient mice with prostate-specific knockout of Ets2 exhibited marked progression of prostate adenocarcinomas that was partly attributed to activation of MAPK signaling.
MET amplification was associated with adenocarcinomas (P = 0.007), high-grade tumors (P = 0.003), more sites of metastasis, higher BRAF mutation, and PTEN loss (all P < 0.05).
Noteworthy clinicopathologic correlations between PTEN transcriptional up/down-regulation and young age (p=0.0081, 61.7+/-8.7years versus 66.1+/-8.1years), smoking (p=0.032) and less differentiated adenocarcinomas (p=0.013) were identified.
Analysis of prostate cancer progression in transgenic adenocarcinoma of mouse prostate mice bred to Pten(+/-) heterozygous mice, coupled with analysis of the Pten gene and protein in the resulting tumors, reveals that haploinsufficiency of the Pten gene promotes the progression of prostate cancer in this model system.
Here, we found that conditional overexpression of Bmi1 in mice induced prostatic intraepithelial neoplasia, and elicited invasive adenocarcinoma when combined with PTEN haploinsufficiency.
Multivariate analysis showed SDC (p = .002) to be the strongest predictor of lymph node metastasis, followed by MET aberration (p = .009), T3/T4 classification (p = .017), PTEN deletion (p = .042), and adenocarcinoma not otherwise specified (NOS; p = .047).
To explore the spectrum of driver mutations among lung cancer tissues from never smokers, specifically in a population where high lung cancer rates have been attributed to indoor air pollution from domestic coal use, multiplexed assays were used to detect >40 point mutations, insertions, and deletions (EGFR, KRAS, BRAF, HER2, NRAS, PIK3CA, MEK1, AKT1, and PTEN) among the lung tumors of confirmed never smoking females from Xuanwei, China [32 adenocarcinomas (ADCs), 7 squamous cell carcinomas (SCCs), 1 adenosquamous carcinoma (ADSC)].