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Evaluation of global DNA histone modifications in human breast and colon cancer by immunohistochemistry.
Author(s) -
Sandusky George,
Prajapati Shashi,
Yin Jun,
Mintze Karen,
Hanson Jeff,
Pangallo Jenna,
Iversen Phil,
Yamamoto Yumi
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a755-c
Subject(s) - histone h3 , immunohistochemistry , histone , colorectal cancer , breast cancer , cancer research , adenocarcinoma , cancer , medicine , pathology , oncology , biology , dna , genetics
Aberrant changes in post‐translational histone modification have been shown to occur in cancer cells. Although histone modifications have been recently reported to be associated with risk of prostate cancer recurrence, global histone modification in tumor progression remains elusive. In this study, using immunohistochemistry (IHC), we characterized patterns of global histone modifications in 136 clinical specimens from different stages of human tumors of breast and colon. These antibodies included: histone H2AX, H3, H4 and 6 modification‐specific antibodies (H2AX modified: S139‐phos; H3 modified: S10‐phos, K9‐Ace, K18‐Ace, K4 modified: K12‐Ace, K16‐Ace). A decision tree paradigm was used for statistical analysis in evaluating the multiple change of histone modification. In the breast carcinoma cases, only the histone H3, H3‐K18‐Ace, and H4‐K16‐Ace were found to be associated with high grade tumor. There were no changes in the other histone markers between normal breast tissue, localized adenocarcinoma, invasive adenocarcinoma and metastatic carcinoma and various histological grades of breast tumors. Tumors of the colon were split into left and right sides for statistical analysis due to different genetic pathways. In tumors originating from the left colon, H3 and H4‐K12‐Ace were highly associated with high grade and stage tumors, while only H3 was associated with high grade stage tumors originating from the right colon. There were no changes in the other Histone markers between normal colonic tissue, localized adenocarcinoma, invasive adenocarcinoma and metastatic carcinoma, and various histological grades of colon tumors. In conclusion, H3 was observed in high grade and stage tumors of the breast and colon. H4‐K12‐Ace antibody was seen in high grade and stage tumors originating from the left colon. H3‐K18‐Ace and H4‐K16‐Ace were associated with high grade and stage tumors of the breast.