Odontogenic Ameloblast Associated Protein as a Novel Biomarker for Human Breast Cancer

Abstract

Odontogenic Ameloblast Associated Protein (ODAM) is a protein isolated in ameloblasts during odontogenesis. ODAM expression was identified in breast cancer, but its significance remains unknown. The purpose of this study is to determine if ODAM expression can serve as a prognostic marker and provide information regarding treatment in human breast cancer. Breast cancer patients were identified from our tumor registry from 1993 to 2003. Archived breast cancer tissue from 243 patients (stage 0 = 53, stage I = 51, stage II = 53, stage III = 47, stage IV = 39) was stained using monoclonal antibody for ODAM. Presence or absence of immunostaining was correlated with stage, histologic grade, response to chemotherapy, and survival using χ2 and logistic regression analyses. Tumor nuclear staining for ODAM increased with increasing group stage ( P < 0.001). Staining for ODAM did not correlate with histologic grade or chemotherapy ( P = 0.558, P = 0.093). Improved outcomes within each stage were noted with ODAM staining, statistically significant for stages 0, I, and II ( P < 0.001, P = 0.003, P = 0.003) and underpowered for stages III and IV ( P = 0.724, P = 0.059). Survival benefit associated with tumor nuclear staining increased with advancing stage ( P < 0.001). These results show that ODAM predicts survival in breast cancer. Research is ongoing to determine ODAM's clinical utility and role in carcinogenesis.

Nuclear Odontogenic Ameloblast-Associated Protein (ODAM) Correlates with Melanoma Sentinel Lymph Node Metastasis

“…Histological features of the primary tumors were recorded for both the SLNnegative and positive samples, along with overall survival (OS) and recurrence data obtained from our patient database. Archived formalin-fixed paraffin embedded tumor tissues were cut and immunostained with murine monoclonal anti-ODAM antibody 8B4, as previously reported [10] and detailed below.…”

“…The presence or absence of ODAM immunostaining was determined in the neoplastic cells of each case and staining was assessed and reported, for the nucleus only, as negative or positive. Nuclear positivity was defined by the presence of distinct smooth homogenous staining of at least 50% of tumor cell nuclei, and negativity was defined as a near complete lack of nuclear immunostaining in essentially all tumor cells of interest (less than 1% of nuclei) as in previous studies [10]. This was based on the observed distribution of nuclear ODAM staining where positive tumors exhibited staining in essentially all (greater than 90%) cell nuclei while staining was present in less than 1% of cell nuclei in tumors designated as ODAM-negative.…”

“…The protein has been detected in a broad range of epithelial tissues and in multiple human cancers including those of the breast, esophagus, gastric tissues, and bronchial epithelium [8,9]. The potential role of this protein as a marker of disease status and survival in breast cancer has been reported as increased nuclear ODAM staining of primary breast tumors across disease staging [10]. A portion of patients (up to ~13% in late stage) who were ODAM-positive exhibited improved survival compared to stage-matched ODAM-negative breast cancer patients while the remaining bulk (~87%) of late stage ODAMpositive tumor patients did not exhibit a survival benefit, suggesting at least two patients' outcome groups associated with ODAM-expressing breast tumors [10].…”

“…The potential role of this protein as a marker of disease status and survival in breast cancer has been reported as increased nuclear ODAM staining of primary breast tumors across disease staging [10]. A portion of patients (up to ~13% in late stage) who were ODAM-positive exhibited improved survival compared to stage-matched ODAM-negative breast cancer patients while the remaining bulk (~87%) of late stage ODAMpositive tumor patients did not exhibit a survival benefit, suggesting at least two patients' outcome groups associated with ODAM-expressing breast tumors [10]. Based on previous observations that lymph node-positive breast cancer patients are often positive for nuclear ODAM staining, together with the propensity of melanomas to metastasize into regional lymph nodes, we examined ODAM expression in primary tumors and lymph node biopsies of patients with SLN-positive (Stage III) and SLN-negative (Stage I-II) melanoma.…”

Expression pattern of odontogenic ameloblast-associated and amelotin during formation and regeneration of the junctional epithelium

“…This cluster contains a number of genes coding for proteins that C Nishio et al Formation/regeneration of junctional epithelium stabilize Ca and PO 4 ions in body fluids and/or guide CaPO 4 deposition into receptive extracellular matrices (Huq et al, 2005;Kawasaki, 2009). Interestingly, ODAM expression is highly upregulated in a number of epithelial cancers whose tissues of origin do not produce the protein (Solomon et al, 2003;Aung et al, 2006;Kestler et al, 2008), and has been suggested as a biomarker for human breast cancer (Siddiqui et al, 2009). Broad expression profiling revealed that both ODAM (Park et al, 2007;Moffatt et al, 2008) and AMTN (Iwasaki et al, 2005;Moffatt et al, 2006b) are produced by ameloblasts during the maturation stage of amelogenesis.…”