Cytokeratin 7 and especially cytokeratin 17 highlighted the presence of ducts in the hyperplastic lesion, which are not present in adenomas. p16 and p53 were negative and Ki-67 immunostaining demonstrated similar low proliferation indices for normal and hyperplastic glands.
Larger adenoma size, higher frequency of villous structure, loss of proliferation polarity, p53 expression, larger TAM numbers and larger microvessel density (MVD) were detected in Group H than in Group L adenomas.
Histone modifications have been linked to increased p53 expression and longer progression-free survival in pituitary tumors; sirtuins are expressed at higher values in GH-expressing compared to nonfunctional adenomas and correlate inversely with size in somatotrophs.
The correlation between the proliferation indices (Ki-67 and p53 expression levels) and invasiveness and size of pituitary adenomas was investigated in primary operated and recurrent adenomas.
Although gene-to-gene analyses identified genetic alterations such as APC, KRAS and TP53 mutations in colon adenomas, it is largely unknown whether there are any others in them.
The classification of neoplasms of adenohypophysial cells is misleading because of the simplistic distinction between adenoma and carcinoma, based solely on metastatic spread and the poor reproducibility and predictive value of the definition of atypical adenomas based on the detection of mitoses or expression of Ki-67 or p53.
It is suggested that TP53 mutation occurs in the early stages of cancer development from adenoma in both LST-G and LST-NG, but is involved at an earlier stage in LST-NG.
When adjusting for confounders with logistic regression, several significant associations were evident including adenoma size with male sex and p53 reactivity; cavernous sinus invasion with size and elevated MIB-1 proliferation index; suprasellar/subfrontal extension with p53 reactivity; and infrasellar invasion with adenoma size alone.
Formalin Fixed Paraffin Embedded tissue were studied for miRNA expression, KRAS, BRAF, PIK3CA mutations, and immuno-histochemistry for APC and p53 proteins for normal colon (n=11), hyperplastic polyps (n=11), high grade adenomas (n=10), low grade adenomas (n=34) and adenocarcinoma (n=13).
Together, this may suggest that two molecular pathways, intermediate methylation associated with KRAS mutations and LST-G morphology, and low methylation associated with CTNNB1 activation and LST-NG morphology, might be involved in LST development, and that involvement of TP53 mutations could be important in both subtypes in the development from adenoma to cancer.
These methylation epigenotypes, with specific genomic aberrations, are mostly completed by the adenoma stage, and additional molecular aberration, such as TP53 mutation, is suggested to lead to cancer development with the corresponding epigenotype.
The fetal zone of the adrenal cortex is believed to be one of the tissues most susceptible to adenoma or carcinoma formation due to loss of p53 function.
In addition, NCOA3, MYC, EGFR, and RAB20 amplifications, as well as TP53 deletions correlated with increased DNA stem line values and/or aneuploidy in adenomas (P<0.05).
Despite the aggressive features of massive size and cavernous sinus invasion, mitotic rates and immunohistochemistry (IHC) labeling for p53 and MIB-1, features alleged to be associated with atypical adenomas, were minimally increased.
Alterations of APC, KRAS and TP53 were observed in a higher percentage of adenocarcinomas compared to adenomas (P<0.05) indicating that the alterations accumulated with malignancy.
Five specific "malignant" events (gain of 8q, 13q, and 20q and loss of 17p and 18q) and aberrant staining for p53 and SMAD4 were all increased in the adenoma fractions of carcinoma cases compared with pure adenomas.