Increased MACC1 levels in tissues and blood identify colon adenoma patients at high risk.

BACKGROUND: Colorectal cancer is a preventable disease if caught at early stages. This disease is highly aggressive and has a higher incidence in African Americans. Several biomarkers and mutations of aggressive tumor behavior have been defined such as metastasis-associated in colon cancer 1 (MACC1) that was associated with metastasis in colorectal cancer patients. Here, we aim to assess colon tissue MACC1 protein and circulating MACC1 transcripts in colon preneoplastic and neoplastic African American patients. METHODS: Patients' tissue samples (n = 143) have been arranged on three tissue microarrays for normal (n = 26), adenoma (n = 68) and cancer (n = 49) samples. Immunohistochemistry was used to detect MACC1 expression. Blood samples (n = 93) from normal (n = 45), hyperplastic (n = 15) and tubular adenoma (n = 33) patients were used to assess MACC1 transcripts using qRT-PCR. Distribution of continuous variables was tested between different diagnoses with Kruskal-Wallis test. Categorical variables were tested by Chi square test. We assessed the prognostic ability of IHC staining by calculating area under receiver operating characteristics curve (ROC) for adenoma and cancer separately. Differences between groups in terms of MACC1 transcript levels in plasma were calculated by using non-parametric (exact) Wilcoxon-Mann-Whitney tests. We performed all calculations with SPSS, version 21. RESULTS: In patient tissues, there was a statistically significant difference in MACC1 expression in normal vs. adenoma samples (p = 0.004) and normal vs. cancer samples (p < 0.001). There was however no major difference in MACC1 expression between adenoma vs. cancer cases or tubular adenomas vs tubulovillous adenomas. The area under the curve for both normal vs. adenoma and normal vs. cancer cases were 70 and 67 %, respectively. MACC1 expression was not correlated to age, gender or anatomical sample location. In patient plasma, MACC1 transcripts in adenoma patients were significantly higher than in plasma from normal patients (p = 0.014). However, the difference between normal and hyperplastic plasma MACC1 transcripts was not statistically significant. CONCLUSION: Metastasis-associated in colon cancer 1 is expressed at early stages of colorectal oncogenesis within the affected colonic tissue in this patient cohort. The plasma transcripts can be used to stratify African American patients at risk for potential malignant colonic lesions.

Association between Diverticular Disease and Pre-Neoplastic Colorectal Lesions in an Urban African-American Population.

BACKGROUND: It is unclear whether there is a shared pathway in the development of diverticular disease (DD) and potentially neoplastic colorectal lesions since both diseases are found in similar age groups and populations. AIM: To determine the association between DD and colorectal pre-neoplastic lesions in an African-American urban population. METHODS: Data from 1986 patients who underwent colonoscopy at the Howard University Hospital from January 2012 through December 2012 were analyzed for this study. The presence of diverticula and polyps was recorded using colonoscopy reports. Polyps were further classified into adenoma or hyperplastic polyp based on histopathology reports. Multiple logistic regression was done to analyze the association between DD and colonic lesions. RESULTS: Of the 1986 study subjects, 1,119 (56%) were females, 35% had DD and 56% had at least one polyp. There was a higher prevalence of polyps (70 vs. 49%; OR = 2.3; 95% CI: 1.9-2.8) and adenoma (43 vs. 25%; OR = 2.0; 95% CI: 1.7-2.5) in the diverticular vs. non-diverticula patients. Among patients who underwent screening colonoscopy, the presence of diverticulosis was associated with increased odds of associated polyps (OR = 9.9; 95% CI: 5.4-16.8) and adenoma (OR = 5.1; 95% CI: 3.4-7.8). CONCLUSION: Patients with DD are more likely to harbor colorectal lesions. These findings call for more vigilance on the part of endoscopists during colonoscopy in patients known to harbor colonic diverticula.

Mixed and nonvaccine high risk HPV types are associated with higher mortality in Black women with cervical cancer.

We studied the incidence of HPV genotypes in mostly Black women with cervical carcinoma and correlated histopathologic tumor characteristics, immune markers and clinical data with survival. Disease-free survival (DFS) and overall survival (OS) were recorded for 60 months post-diagnosis. Fifty four of the 60 (90%) patients were Black and 36 (60%) were < 55 years of age. Of the 40 patients with typeable HPV genotypes, 10 (25%) had 16/18 HPV genotypes, 30 (75%) had one of the non-16/18 HPV genotypes, and 20 (50%) had one of the 7 genotypes (35, 39, 51, 53, 56, 59 and 68) that are not included in the nonavalent vaccine. Mixed HPV infections (≥ 2 types) were found in 11/40 (27.5%) patients. Patients infected with non-16/18 genotypes, including the most common genotype, HPV 35, had significantly shorter DFS and OS. PD-L1 (p = 0.003), MMR expression (p = 0.01), clinical stage (p = 0.048), histologic grade (p = 0.015) and mixed HPV infection (p = 0.026) were independent predictors of DFS. A remarkably high proportion of cervical cancer cells in our patients expressed PD-L1 which opens the possibility of the use of immune checkpoint inhibitors to treat these cancers. Exclusion of the common HPV genotypes from the vaccine exacerbates mortality from cervical cancer in underserved Black patients.

Gastrointestinal Lesions in African American Patients With Iron Deficiency Anemia.

BACKGROUND: Iron deficiency anemia (IDA) is a frequent disorder that is associated with many serious diseases. However, the findings of an evaluation of IDA-associated gastrointestinal disorders are lacking among African American patients. AIM: To determine the most prevalent gastrointestinal lesions among African American patients with IDA especially in young men. METHODS: We reviewed medical records (n = 422) of patients referred for evaluation of IDA from 2008 to 2012. Iron deficiency anemia was diagnosed using clinical laboratory tests. The results of esophagogastroduodenoscopy, colonoscopy, and pathology specimens along with demographic data were abstracted and analyzed using Stata. RESULTS: The mean age was 61.9 years, and 50.5% were women. In total, 189 patients (45%) had gross gastrointestinal (GI) bleeding. The most frequent diagnoses were gastritis (40%), benign colonic lesions (13%), esophagitis (9%), gastric ulcer (6%), and duodenitis (6%). GI bleeding was significantly more frequent in men (P = 0.001). Benign and malignant colonic lesions were significantly more present among older patients: 16% vs 6% (P = .005) and 5% vs 0% (P = .008), respectively. Colitis was more prevalent in younger patients (⩽50): 11% vs 2% (P = .001). In patients with gross lower GI bleeding, the top diagnoses were gastritis (25%), benign colon tumors (10%), and duodenitis (6%). Colon cancer was diagnosed among 15 patients, and all these patients were older than 50 years of age. CONCLUSIONS: Gastritis and colonic lesions are most common associated lesions with IDA among African Americans. So bidirectional endoscopy is required for unrevealing of the cause of IDA in asymptomatic patients.