It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumours with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA.
Current data indicate that each of these histologic subtypes is associated with distinct morphologic and molecular genetic alterations: high-grade serous and possibly endometrioid carcinomas most probably arise from surface epithelial inclusion glands with TP53 mutations and dysfunction of BRCA1 and/or BRCA2; low-grade serous carcinomas probably arise in a stepwise fashion in an adenoma-borderline tumor-carcinoma sequence from typical to micropapillary borderline tumors to low-grade invasive serous carcinoma via activation of the RAS-RAF signaling pathway secondary to mutations in KRAS and BRAF; mucinous carcinomas arise via an adenoma-borderline tumor-carcinoma sequence with mutations in KRAS; low-grade endometrioid carcinomas arise from endometriosis via mutations in CTNNB1 (the gene encoding beta-catenin) and PTEN.
The present study has assessed the in situ expression of PTEN mRNA and protein in 26 prostate intraepithelial neoplasias (PINs), 58 primary prostate carcinomas, and 15 metastases.
Loss of PTEN function has been implicated in the progression of several types of cancer, but the correlation between loss of PTEN expression and advanced carcinomas is not well established.
Immunohistochemical analyses of ER expression in mammary carcinomas arising in PTEN heterozygous knockout mice did not demonstrate a reduction in ER immunoreactivity, in comparison to wild-type mice.
To investigate the role of PTEN and matrix metalloproteinase-7 (MMP-7) expression in tumorigenesis and progression of gastric carcinoma, their expression in 113 gastric carcinomas was studied by immunohistochemistry.
Expression of PTEN transcript was abnormally low in 5 of 15 (33%) cell lines and 20 of 55 (36%) primary carcinomas, whereas 0 of 71 noncancerous tissues including 16 benign tumors showed altered expression.
These conditions recently have been molecularly elucidated, and some of the genes responsible for them (including STK11/LKB1 and PTEN, the genes responsible for PJS and CD, respectively) have already been investigated in series of sporadic ovarian lesions, mostly carcinomas.
CGH analysis demonstrated that all four tumors (100%) showed chromosomal copy number loss around the locus of this gene, whereas four (57%) of seven tumors with PTEN/MMAC1 mutations showed chromosomal loss or double mutations in MI- carcinomas.
The p53 gene appears to be involved in the process of transformation to the anaplastic phenotype and the PTEN gene in the development of follicular adenomas but not carcinomas.
Somatic mutations in the PTEN gene were identified in 4 of 20 ovarian endometrioid carcinomas (20.0%), 2 of 24 clear cell carcinomas (8.3%), and 7 of 34 solitary endometrial cysts (20.6%).
Further, one in 20 unselected cervical carcinomas was found to have a germline PTEN mutation; it is unclear whether the patient with this mutation had Cowden disease or a related syndrome.
Although somatic intragenic PTEN mutations have rarely been found in benign and malignant sporadic thyroid tumors, loss of heterozygosity (LOH) has been reported in up to one fourth of follicular thyroid adenomas (FAs) and carcinomas.