Background: Colorectal cancer (CRC) as the second most common cancer in western world has different prognostic basis in contrast to other cancers. Its pathologic staging is the main prognostic factor. Recently, MACC1 has been proposed as an effective marker for identifying patients at high risk for the development of distant metastases when MACC1 is highly expressed in the not (yet) metastasized primary tumor. Aims and Methods: We aimed to assess the cellular and sub-cellular expression of MACC1 in age matched normal, adenomatous and cancerous colonic tissue samples. Samples were recruited from pathology department of Howard University Hospital. The Tissue Micro Array (TMA) sections were made from all duplicated samples and put in three different TMA slides as normal matched (n=44), adenomatous (n=60) and adenocarcinoma (n=36). Total of 140 samples were stained for MACC1 by Immuno-Histo-Chemistry method. Then, all three TMA were read by two pathologists including one GI pathologist. The expression were reported as staining 0, 1, 2, 3, 4 which refer to none, less than 10%, 10-25%, 25-50%, 50-75%, >75%, respectively. Sub-cellular staining was reported as nuclear, cytoplasmic, or both. Results: Of 140 samples, 36 were adenocarcinomas (mean age: 64.3; M/F: 16/20); 60 adenomatous (mean age: 64.8; M/F: 31/29); 44 normal controls (mean age 65.8; M/F: 22/22). Adenocarcinomas received score 4 in 86.1% of cases which was significantly higher (p<0.05) than normal (15.9%) and adenomatous (28.3%) cases. MACC1 stained more in cytoplasm (88.6%) in contrast to normal (44.7%) and adenomatous cases (32.1%) with P < 0.05. Observationally, high grade adenomas had higher scores (3 or 4) than low grade ones (P=0.1). Of total 18 patients with stage 3 and/or 4, 14 scored 4 and had cytoplasmic stainning. Conclusions: Our data showed that MACC1 not only can be a prognostic and pathological marker to differentiate high grade from low grade adenoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3871. doi:10.1158/1538-7445.AM2011-3871

Back ground: African Americans (AAs) are known to display a higher rate and even earlier age of colorectal cancer (CRC) than in the general population. Genetically, 10-12% microsatellite instability (MSI) cases involved in CRC development. However, if it occurs below the age of 50 it could be suspicious of Lynch syndrome. Aims and methods: We aimed to assess the role of MSI in pathogenesis of sporadic colorectal cancer in young African American. The CRC patients in this study were less than 50 years and referred to Howard University Hospital from 2005 to 2008. The medical records (n=50) as well as the pathology reports were reviewed. The MSI status was assessed in a multiplex PCR targeting 5 markers: BAT25, BAT26, NR21, NR27 and NR24. The PCR products were analysed in an Applied Biosystems Gene Scan 3130 machine. Samples with two or more instable markers were labeled MSI-H, with one instable marker: MSI-L and no stable marker: MSS. The presence or absence of expression of four DNA MMR proteins: MLH1, PMS2, MSH2 and MSH6 were evaluated using immunohistochemistry on a Tissue Microarray (TMA, n=26, duplicate) consisting (stage1: 3; stage 2: 6; stage3: 5; stage4: 4).TMA IHC staining were read by two different pathologists who were not aware of the patient clinical status and were scored thus in an objective manner. Two patients were MSI-L and one MSI-H. The response to 5-FU based therapy was reported. Results: Twenty six patients [age, median: 44.5; age range: 26-49; male, 17 (65.4%)] were enrolled in the study. Seven out of 13 available data had family history of CRC. Fourteen CRC cases were left sided. MSI analysis revealed that out of 24 patients: one was MSI-H and two were MIS-L and the rest were MSS. The MSI high patient and one of the MSI low had family history of CRC. MLH1, PMS2, MSH2 and MSH6 were not expressed in 7 (26.9%), 1 (3.8%), 0 (0%) and 5 (19.2%) of tumors, respectively. IHC confirmed the MSI-H tumor. There was a recurrence with lung and brain metastases at 72 months in one of the MSI-L patients following adjuvant chemotherapy with 5 Fluorouracil and Leucovorin. Discussion: Our results show that MSI is not a major pathway in tumorgenesis of sporadic CRCs in young AAs and we may need to study chromosomal instability or CpG Island methylator phenotype as alternative pathways which occur in African Americans and make them present the disease at younger age and advanced stage. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3884. doi:10.1158/1538-7445.AM2011-3884

Background: It has become common wisdom that Helicobacter pylori (HP) infection is linked to gastric cancer. However, its involvement in colorectal cancer (CRC) is still under investigation. The trophic effects of induced hypergastrinemea on colon homeostasis as well as HP direct effects on the colon mucosa might play a role in CRC. Methods: We previously reported that epidemiological data in African American patients (n=1262, >40 years old) who underwent bidirectional gastrointestinal endoscopy show an HP association with colon polyps formation. To substantiate this linkage, we used serological testing on healthy (n=94) and colon polyp (n=95) patients for anti-HP and anti-CagA antibodies to further confirm our epidemiological findings. Microarray used to detect the Gut flora including HP using 16rDNA from stool (n=12) of healthy and colon adenomas. Results: The healthy individuals had an average age of 63.7 (SD=9.80) while the polyp patients had an average age of 62.8 (SD=9.7). The gender distribution was 42/52 and 41/54 in the two groups for males and females, respectively. As such, the two groups were age and sex matched. In the polyp patients, 55.6% was HP-positive while there was only 48.8% positive in the control group (p=0.30 for this difference). Cag A positive samples were 73.3% in polyp patients and 67.5% in healthy individuals (p = 0.5). Gut flora analysis using a 16S rDNA microarray from stool (n=12) samples revealed the presence of HP signals in healthy and colon adenomas analyzed samples. Conclusion: HP seems to be associated with an increased risk of colon adenoma. However, whether HP is a colon inhabitant and participant in colon carcinogenesis or just a gastric wash-out is under investigation in normal and tumor colon biopsies’ gut flora studies. Large sample size is needed to confirm the above observed trend of a possible association of HP with CRC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1884. doi:10.1158/1538-7445.AM2011-1884