Cancer HDAC Results
Gastric Carcinoma HDAC1
• 78% of cases a moderate or strong acetylation of Histone H4.

•Over expression HDAC1, HDAC2 and HDAC 6 in 60%, 32% and 15% case respectively.

•Over expression HDAC6 show improved survival times that is independent of tumor aggressiveness [30]

Colorectal Carcinoma HDAC1
•Moderately expression of Class I HDACs 1, 2 and 3 in glandular and foveolarantral and corpus gastric epithelium.

•Over Expression of HDAC2 in tumors with nodal metastases and advanced tumor stage.

•HDAC2 protein expression had independent prognostic impact on overall survival [OS][31,32].

•Low acetylation of histone H4 in Class I HDACs [33].

•Over expression of HDAC1 showed a negative association with patient survival and acetylation on H3K9 and H4K16 did not correlate with patient prognosis.

•Hyperacetylation of H3 was associated with poor tumor grade and diffuse type cancers [34].

Hepatocellular Carcinoma    HDAC1
•Over expression HDAC1, 2 and 3 in the level of mRNA and protein with overall protein expression 37% , 58%  and 73% respectively.

•High expression of HDAC1 and HDAC2 was associated with enhanced tumor cell proliferation and negative prognostic impact on OS, only HDAC2 had an independent prognostic impact [35].

•Negative prognostic impact of high HDAC1 mRNA levels on OS [36]

•Loss of expression of HDACI isoforms [37].

Pancreatic Carcinoma HDAC1 •Over HDAC1 protein expression in hepatocellular carcinomas that correlated with higher tumor stage and poor tumor differentiation [38].

•Class II HDACs 4,5,6,7 and 10 , higher expression levels of both mRNA and protein have been reported in HCC[39].

Brain Tumors HDAC9
•High HDAC1 expression in 56% of pancreatic carcinomas that had significant prognostic impact on OS [40,41].

Prostate Carcinoma HDAC1
•Expression class I HDAC mRNA were lower than class II and IV isoforms.

•Low expression of HDAC9 (class II) and HDAC11 (class IV) mRNAs in high-grade tumors compared to low-grade tumors.

•High histone H3 acetylation levels in high-grade glioblastoma compared to low-grade gliomas[42].

Ovarian Carcinoma HDAC1
•High expression HDAC1, 2 and 3 protein in prostate adenocarcinomas and expression patterns these isoforms in high-grade Prostatic Intraepithelial Neoplasia(PIN) paralleled with invasive cancers.

•Disease-free survival (DFS) in patients with high-level HDAC2 protein expression reduced.

•Strong HDAC1 and HDAC2 protein expression associated with high Gleason grade and with high proliferative capacity [43].

•High expression HDAC1 in hormone refractory cancers [44].

•High expression HDAC4 in benign prostate hyperplasia,  prostate cancers and hormone refractory cancers [45].

Endometrial Carcinoma HDAC1
•Over expression class I HDACs in ovarian carcinoma that positivity rates differ in tumor subtypes such as mucinous carcinomas (71%), high-grade serous (64%), clear cell (54%) and endometrioid subtypes (36%) and expression was usually higher in strongly proliferating tumors.

•Disease Specific patient Survival (DSS) in serous, mucinous, and clear cell carcinomas had no statistical significant but in endometrioid ovarian cancer had negative impact on patient survival [46,47].

Non-Small Cell Lung Carcinoma (NSCL)

•Over expression class I HDAC isoforms in endometrial carcinomas and like in ovarian carcinomas, clear cell (83%) and serous subtypes (69%) showed significantly higher expression rates of class I HDACs than endometrioid carcinomas.

•Strong HDAC1 protein expression but no HDAC2 and HDAC3 were associated with poor prognosis.

•None of the class I HDACs had independent prognostic impact on DSS [47].

Breast Carcinoma HDAC1
•Downregulation of HDAC4 mRNA in lung tumors [48,49].

•Overexpression HDAC1 in stage III/IV tumors compared to stage I/II tumors [50].

•Overexpression HDAC class I in NSCLC.

•mRNA HDAC7expression levels in node-negative low stage tumors higher than advanced tumors with nodal metastasis.

•RNA level class I HDAC expression had no impact on overall patient prognosis [51].

•High mRNA expression of class II HDACs 4,5,6,7 and 10 was predictive of a better prognosis.

•Deacetylation of H3K9 in stage I NSCLC conferred a better prognosis, the same was true for patients with NSCLCs stage II and deacetylation on H2AK5 [52].

    •HDAC1 and HDAC3 protein expression was high in estrogen and progesterone receptor positive tumors.

•High HDAC1 mRNA expression predicted better OS and DFS.

•HDAC1 expression predicted significantly DFS better than OS in patients with invasive breast cancers.

•HDAC3 protein expression had no impact on either DFS or OS.

•RNA expression of HDAC1 was not an independent predictor of either OS or DFS [53,54].

•Reported no differences in OS and DFS in HDAC6 expression, however, and in the subgroup of ER positive patients with strong HDAC6 expression was an independent prognosticator of better DFS [55]

•Class II HDAC6 expression was positive in breast cancer and prominent in small, low-grade, estrogen and progesterone receptor positive tumors compared to larger high-grade hormone receptor negative cancers [55].

•High HDAC6 protein had a negative prognostic influence [56].

Table 2: Histone deacetylase (HDAC) expression in human tumors.