Introduction: Several lines of evidence suggest the contribution of cancer stem cells (CSCs) to the tumorigenicity of bladder cancer. Although CD133 and CD24 CSC biomarkers are associated with survival disadvantages in some cancers, the biological attributes of a specific tumor alters the expression of these markers and any associated phenotypic characteristics. Aim: To analyze CD133 and CD24 expression and their different phenotypes in urinary bladder carcinoma. Material and methods: Expression of CD133 and CD24 and their divergent phenotypes were analyzed in patients with urinary bladder carcinoma (n=60) and correlated with clinicopathological parameters. Results: CD133 + and CD24 + tumor cells were more frequent in high grade, less differentiated carcinomas (18/22, and 15/17, p =0.022 and 0.01, respectively), muscle invasive tumors (20/22, p =0.017 and 17/17, p =0.001, respectively), and tumors with advanced stage ( p =0.001 and 0.007, respectively). The expression of CD24 slightly correlated with lymphovascular invasion ( p =0.04), whereas CD133 was associated with distant metastasis. The CD133 + CD24 + phenotype exhibited more aggressive tumorigenic behavior than other phenotypes. Conclusion: CD133 + and CD24 + cells correlated with determinants of aggressive behavior and may be involved in tumor progression and distant metastasis. The CD133 + subpopulation is likely to have a more potent tumorigenic capacity. Although divergent, the strong correlation between the two populations may support phenotypic plasticity among them. Compared to the CD133 + CD24 − and CD133 − CD24 + phenotypes, the CD133 + CD24 + phenotype is the most aggressive. These putative biomarkers can potentially aid in the selection of high-risk patients for more aggressive targeted therapy.
Loss in apoptosis competence often results in augmented genomic instability contributing to carcinogenesis. Cytochrome c oxidase subunit I (CcOI) can help assess apoptosis resistance in paraffin-embedded biopsies. In total, 50 colorectal cases including 10 control cases of colectomy for non-neoplastic condition, 15 cases of adenomatous colorectal polyps, and 25 cases of colorectal carcinoma were investigated in this retrospective study for immunohistochemical expression of CcOI. The staining pattern of CcOI was assessed and indices of aberrant expression were calculated as crypt-restricted loss and overall decreased immunostaining (ODI). ODI calculated in the adenocarcinoma tumor tissue was designated as Tr ODI. The crypt-restricted loss and ODI indices of the aberrant CcOI expression are significantly higher in the adenomatous polyps group (2.5% and 47.54%) and in the non-neoplastic mucosa among adenocarcinoma group (2.78% and 49.1%) when they are compared with the control group (0.55% and 7.32%) (P<0.001). A highly significant correlation was noted between Tr ODI and the tumor grade, the nodal status, and the stage among adenocarcinomas. In conclusion, colonic tumors arise in a field of crypts with aberrations in CcOI expression. This aberration is linked to biologically aggressive tumors. CcOI immunostaining may be applied on mucosal samples from patients with colonic adenomatous polyps and patients with previous cancer colon resection to determine individuals who are in need for frequent colonoscopies and/or chemopreventive strategies. Future follow-up studies are warranted to determine the level of expression predictive of recurrence or progression.
Screening mammography improved early detection of breast cancer and since then, the percentage of patients with node involvement is declining. Sentinel lymph node biopsy (SLNB), although helpful in the diagnostic armamentarium of these patients, has consequential limitations. In these patients, moreover, lymphatic invasion (LI) is of utmost importance to determine the risk of local recurrence. To find an adjuvant histologic approach to assist in pre-operative analysis of the patient's risk for having LI and thus sentinel ± non-sentinel axillary lymph node metastasis, one hundred and twenty patients with early invasive duct carcinoma without axillary lymph node metastasis were evaluated. Logistic regression predictive models were built from 80 patients and validated in the remaining 40 patients. The final stepwise multi-regression analysis identified four sensitive models. In the validation group, model 1 [applicable to tumors grade 3 having micropapillary differentiation (MPD)] correctly identified 92.31% of patients with LI and confirmed LI [positive predictive value (PPV) = 83%], but with moderate sensitivity. Model 2 [applicable to tumors without MPD], model 3 [applicable to tumors grade 1/2], and model 4 [applicable to tumors grade 1/2 having no MPD] all had moderate PPV and a high negative predictive value (NPV) rendering these models reliable negative tests. However, as they had high sensitivity, positive results confirm the presence of LI. Patient with tumors grade 3 and MPD might need SLNB and/or axillary lymph node dissection (ALND). Patients having tumors grade 1/2, size <2 cm, and no MPD nor extensive retraction artifact, SLNB and/or ALND could be omitted. In tumors grade 1/2 (model 2) and those without MPD (model 3), the proposed models are reliable negative tests rather than a definitive positive one.
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