Performance of a Commercially Available MAL Antibody in the Diagnosis of Primary Mediastinal Large B-Cell Lymphoma.

Myelin and lymphocyte (MAL) protein has been previously reported as a highly specific marker for distinguishing primary mediastinal large B-cell lymphoma (PMBL) from diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS). However, there has not been a commercially available MAL antibody for immunohistochemistry. We identified a commercially available MAL monoclonal antibody and evaluated it by immunohistochemistry on 43 cases of PMBL and 63 cases of DLBCL, NOS. We also compared this with a CD200 antibody that was previously reported useful in distinguishing PMBL and DLBCL, NOS. A threshold of 10% positive tumor cells was used to determine positive protein expression. MAL was expressed in 72% cases of PMBL and 0% of cases of DLBCL, NOS (sensitivity=72%, specificity=100%). CD200 was expressed in 81% of PMBL cases and 13% of DLBCL, NOS cases (sensitivity=81%, specificity=87%). To our knowledge, this is the first report on the utility of a commercially available MAL monoclonal antibody in the diagnosis of PMBL. There is a high specificity with good sensitivity in distinguishing PMBL from DLBCL, NOS, similar to previous studies with a noncommercial source. This antibody will likely prove useful in identifying cases of PMBL in routine practice.

Decreased MALL expression negatively impacts colorectal cancer patient survival.

The aim of the present study was to determine whether MALL expression is associated with colon cancer progression and patient survival. MALL mRNA expression was reduced in the tumor tissues of 70% of the colon cancer patients and 75% of the rectal cancer patients as compared to their normal tissues. MALL protein was also significantly reduced in the tumor tissues of colon cancer patients (P < 0.001). Increased LOH and methylation of MALL was observed in tumor tissues as compared to normal tissues. Reduced MALL expression was associated with vessin invasion, disease recurrence and metastasis or death (P ≤ 0.027). Furthermore, patients with MALL-negative tumors had significantly decreased overall survival (OS) and disease-free survival (DFS) (P < 0.008 and P < 0.011, respectively). Univariate analysis indicated that MALL expression was significantly associated with OS and DFS. Finally, overexpression of MALL suppressed HCT116 and SW480 cell proliferation and inhibited HCT116 migration. MALL may play a role in colorectal cancer progression as suppression of its expression in tumor tissues negatively impacts colorectal cancer patient survival. Further analyses are required to determine if reduced MALL expression is due to LOH and/or methylation.

MAL2 expression predicts distant metastasis and short survival in pancreatic cancer.

BACKGROUND: Pancreatic cancer is associated with a devastating prognosis, partially because of its aggressive metastatic ability. Identification of prognostic markers of metastasis would be useful in the clinical management of postoperative patients with pancreatic cancer. Mal, T-cell differentiation protein 2 (MAL2) has been identified as a molecule predictive of metastases; the clinical relevance of MAL2 in pancreatic cancer is unknown. METHODS: Orthotopic human pancreatic cancer xenografts from the pancreatic cancer cell line SUIT-2 were established in nude mice. Only liver metastasis was harvested and cultured. These metastatic cycles were repeated 5 times to establish a highly metastatic cell line, termed metastatic SUIT-2 (MS). We investigated proliferation and motility of MS cells compared with those of the parent SUIT-2. Microarray analysis was performed to investigate differences in gene expression. We also performed immunohistochemical analysis of 89 formalin-fixed, paraffin-embedded human pancreatic cancer tissue samples to investigate the clinical significance of MAL2 expression. RESULTS: MS cells showed a greater metastatic rate after orthotopic implantation than parental SUIT-2. MS cells had increased motility but decreased proliferation compared with parental SUIT-2. Microarray analyses showed that 26 genes were significantly upregulated (>10-fold) in MS cells compared with parental SUIT-2, particularly MAL2 expression. Immunohistochemical analysis showed that high expression of MAL2 was associated with a lesser survival of postoperative patients (P = .03) and a high rate of distant metastasis (P = .008). CONCLUSION: We characterized a newly established pancreatic cancer cell line with highly metastatic potential. MAL2 is a promising predictive marker for distant metastasis and short survival in patients with resected pancreatic cancer.