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Int J Clin Exp Pathol 2010;3(8):768-774
Original Article
Correlation between mcl-1 and pakt protein expression in colorectal cancer
Evita B. Henderson-Jackson, James Helm, Masoumeh Ghayouri, Ardeshir Hakam, Aejaz Nasir, Marino Leon, Marilyn Bui, Timothy Yeatman,
Domenico Coppola
Departments of Oncologic Sciences; Anatomic Pathology; Gastrointestinal Oncology; Biostatistic; Program of Experimental Therapeutics; Moffitt
Cancer Center and Research Institute; and 6Department of Pathology, at the University of South Florida, School of Medicine; Tampa, Florida,
USA.
Received September 25, 2010; accepted October 11, 2010; available online October 12, 2010
Abstract: Mcl-1 inhibits apoptosis in well-differentiated cells by sequestering BAD, BID, and BAX and other apoptotic molecules. pAKT blocks
apoptotsis by facilitating the interaction of BAD with BCL-XL . Expression of pAKT and Mcl-1 have been described in colon cancer, however, the
relationship between pAKT and Mcl-1 has not. Mcl-1 and pAKT immunohistochemistry was performed using colorectal cancer tissue
microarray (TMA). The Holm step-down method was used to adjust for multiple testing. Mcl-1 and pAKT scores, stage, and grade were
compared using Spearman’s correlation coefficient. Metastasis and no metastasis groups were compared using the Wilcoxon rank sum test.
Mcl-1 and pAKT scores were compared for normal colorectal mucosa (NR), adenoma (AD), and colorectal cancer (CRC) cohorts. The mean
(SD) pAKT expression in NR (14) was 2.0 (1.4), in AD (8) was 3.0 (1.7), and in CRC (101) was 5.6 (2.4). These differences were statistically
significant. For Mcl-1 the mean (SD) expression was 4.1 (1.7) in NR, 3.2 (1.2) in AD, and 3.3 (2.6) in CRC. Mcl-1 and pAKT scores were directly
correlated during various stages of colon carcinogenesis (p = 0.04). Mcl-1 showed direct correlation with tumor grade (p = 0.001) and tumor
stage (p = 0.02) and with presence of metastasis (p = 0.008). We report the correlation of Mcl-1 protein expression with higher grade and stage
in colorectal cancer. Mcl-1 correlated also with pAKT expression. We also report the up regulation of pAKT during the transition from NR to
CRC. (IJCEP1009007).
Keywords: Mcl-1, pAKT, colon adenocarcinoma, normal colon, immunohistochemistry
Full text PDF
Address all correspondence to:
Domenico Coppola, MD
Anatomic Pathology Division
Moffitt Cancer Center and University of South Florida
12902 Magnolia Drive,
Tampa, Florida 33612-9497.
Phone: (813)745-3275; Fax: (813)745-1708;
E-mail: Domenico.Coppola@moffitt.org.
Original Article
Correlation between mcl-1 and pakt protein expression in colorectal cancer
Evita B. Henderson-Jackson, James Helm, Masoumeh Ghayouri, Ardeshir Hakam, Aejaz Nasir, Marino Leon, Marilyn Bui, Timothy Yeatman,
Domenico Coppola
Departments of Oncologic Sciences; Anatomic Pathology; Gastrointestinal Oncology; Biostatistic; Program of Experimental Therapeutics; Moffitt
Cancer Center and Research Institute; and 6Department of Pathology, at the University of South Florida, School of Medicine; Tampa, Florida,
USA.
Received September 25, 2010; accepted October 11, 2010; available online October 12, 2010
Abstract: Mcl-1 inhibits apoptosis in well-differentiated cells by sequestering BAD, BID, and BAX and other apoptotic molecules. pAKT blocks
apoptotsis by facilitating the interaction of BAD with BCL-XL . Expression of pAKT and Mcl-1 have been described in colon cancer, however, the
relationship between pAKT and Mcl-1 has not. Mcl-1 and pAKT immunohistochemistry was performed using colorectal cancer tissue
microarray (TMA). The Holm step-down method was used to adjust for multiple testing. Mcl-1 and pAKT scores, stage, and grade were
compared using Spearman’s correlation coefficient. Metastasis and no metastasis groups were compared using the Wilcoxon rank sum test.
Mcl-1 and pAKT scores were compared for normal colorectal mucosa (NR), adenoma (AD), and colorectal cancer (CRC) cohorts. The mean
(SD) pAKT expression in NR (14) was 2.0 (1.4), in AD (8) was 3.0 (1.7), and in CRC (101) was 5.6 (2.4). These differences were statistically
significant. For Mcl-1 the mean (SD) expression was 4.1 (1.7) in NR, 3.2 (1.2) in AD, and 3.3 (2.6) in CRC. Mcl-1 and pAKT scores were directly
correlated during various stages of colon carcinogenesis (p = 0.04). Mcl-1 showed direct correlation with tumor grade (p = 0.001) and tumor
stage (p = 0.02) and with presence of metastasis (p = 0.008). We report the correlation of Mcl-1 protein expression with higher grade and stage
in colorectal cancer. Mcl-1 correlated also with pAKT expression. We also report the up regulation of pAKT during the transition from NR to
CRC. (IJCEP1009007).
Keywords: Mcl-1, pAKT, colon adenocarcinoma, normal colon, immunohistochemistry
Full text PDF
Address all correspondence to:
Domenico Coppola, MD
Anatomic Pathology Division
Moffitt Cancer Center and University of South Florida
12902 Magnolia Drive,
Tampa, Florida 33612-9497.
Phone: (813)745-3275; Fax: (813)745-1708;
E-mail: Domenico.Coppola@moffitt.org.
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