Evaluation of lymph node numbers for adequate staging of Stage II and III colon cancer

<p>Abstract</p> <p>Background</p> <p>Although evaluation of at least 12 lymph nodes (LNs) is recommended as the minimum number of nodes required for accurate staging of colon cancer patients, there is disagreement on what constitutes an adequate identification of such LNs.</p> <p>Methods</p> <p>To evaluate the minimum number of LNs for adequate staging of Stage II and III colon cancer, 490 patients were categorized into groups based on 1-6, 7-11, 12-19, and ≥ 20 LNs collected.</p> <p>Results</p> <p>For patients with Stage II or III disease, examination of 12 LNs was not significantly associated with recurrence or mortality. For Stage II (HR = 0.33; 95% CI, 0.12-0.91), but not for Stage III patients (HR = 1.59; 95% CI, 0.54-4.64), examination of ≥20 LNs was associated with a reduced risk of recurrence within 2 years. However, examination of ≥20 LNs had a 55% (Stage II, HR = 0.45; 95% CI, 0.23-0.87) and a 31% (Stage III, HR = 0.69; 95% CI, 0.38-1.26) decreased risk of mortality, respectively. For each six additional LNs examined from Stage III patients, there was a 19% increased probability of finding a positive LN (parameter estimate = 0.18510, p < 0.0001). For Stage II and III colon cancers, there was improved survival and a decreased risk of recurrence with an increased number of LNs examined, regardless of the cutoff-points. Examination of ≥7 or ≥12 LNs had similar outcomes, but there were significant outcome benefits at the ≥20 cutoff-point only for Stage II patients. For Stage III patients, examination of 6 additional LNs detected one additional positive LN.</p> <p>Conclusions</p> <p>Thus, the 12 LN cut-off point cannot be supported as requisite in determining adequate staging of colon cancer based on current data. However, a minimum of 6 LNs should be examined for adequate staging of Stage II and III colon cancer patients.</p

Prognostic Significance and Gene Expression Profiles of p53 Mutations in Microsatellite-Stable Stage III Colorectal Adenocarcinomas

Although the prognostic value of p53 abnormalities in Stage III microsatellite stable (MSS) colorectal cancers (CRCs) is known, the gene expression profiles specific to the p53 status in the MSS background are not known. Therefore, the current investigation has focused on identification and validation of the gene expression profiles associated with p53 mutant phenotypes in MSS Stage III CRCs. Genomic DNA extracted from 135 formalin-fixed paraffin-embedded tissues, was analyzed for microsatellite instability (MSI) and p53 mutations. Further, mRNA samples extracted from five p53-mutant and five p53-wild-type MSS-CRC snap-frozen tissues were profiled for differential gene expression by Affymetrix Human Genome U133 Plus 2.0 arrays. Differentially expressed genes were further validated by the high-throughput quantitative nuclease protection assay (qNPA), and confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and by immunohistochemistry (IHC). Survival rates were estimated by Kaplan-Meier and Cox regression analyses. A higher incidence of p53 mutations was found in MSS (58%) than in MSI (30%) phenotypes. Both univariate (log-rank, P = 0.025) and multivariate (hazard ratio, 2.52; 95% confidence interval, 1.25–5.08) analyses have demonstrated that patients with MSS-p53 mutant phenotypes had poor CRC-specific survival when compared to MSS-p53 wild-type phenotypes. Gene expression analyses identified 84 differentially expressed genes. Of 49 down-regulated genes, LPAR6, PDLIM3, and PLAT, and, of 35 up-regulated genes, TRIM29, FUT3, IQGAP3, and SLC6A8 were confirmed by qNPA, qRT-PCR, and IHC platforms. p53 mutations are associated with poor survival of patients with Stage III MSS CRCs and p53-mutant and wild-type phenotypes have distinct gene expression profiles that might be helpful in identifying aggressive subsets

Robust Synthesis of Targeting Glyco‐Nanoparticles for Surface Enhanced Resonance Raman Based Image‐Guided Tumor Surgery

Surface enhanced resonance Raman (SERS) is a powerful optical technique, which can help enhance the sensitivity of Raman spectroscopy aided by noble metal nanoparticles (NPs). However, current SERS‐NPs are often suboptimal, which can aggregate under physiological conditions with much reduced SERS enhancement. Herein, a robust one‐pot method has been developed to synthesize SERS‐NPs with more uniform core diameters of 50 nm, which is applicable to both non‐resonant and resonant Raman dyes. The resulting SERS‐NPs are colloidally stable and bright, enabling NP detection with low‐femtomolar sensitivity. An algorithm has been established, which can accurately unmix multiple types of SERS‐NPs enabling potential multiplex detection. Furthermore, a new liposome‐based approach has been developed to install a targeting carbohydrate ligand, i.e., hyaluronan, onto the SERS‐NPs bestowing significantly enhanced binding affinity to its biological receptor CD44 overexpressed on tumor cell surface. The liposomal hyaluronan (HA)‐SERS‐NPs enabled visualization of spontaneously developed breast cancer in mice in real time guiding complete surgical removal of the tumor, highlighting the translational potential of these new glyco‐SERS‐NPs

IHC expression patterns of up-regulated genes in <i>p53</i> mutant phenotypes of MS CRCs.

<p><b>a</b>, normal colonic epithelium (NCE) demonstrating moderate cytoplasmic (thick arrow) and weak membrane (thin arrow) FUT3 staining (400 µm). <b>b</b>, CRCs exhibiting strong cytoplasmic (thick arrows) and moderate to weak membrane FUT3 staining (thin arrows) (400 µm). <b>c</b>, CRCs with weak cytoplasmic staining (thin arrows) (400 µm). <b>d</b>, NCE demonstrating weak cytoplasmic TRIM29 staining with a focal punctuate pattern (thin arrows) (400 µm). <b>e</b>, CRCs exhibiting moderate to strong cytoplasmic TRIM29 staining with a punctate pattern on the luminal aspect (thin arrows) (600 µm). <b>f</b>, CRCs with weak cytoplasmic TRIM29 staining (thin arrows) (400 µm). <b>g</b>, NCE demonstrating weak cytoplasmic to complete lack of IQGAP3 staining. [Note: Lymphocytes in the stroma show moderate cytoplasmic staining (thin arrows); the adjacent tumor demonstrates moderate cytoplasmic and nuclear immunostaining (thick arrows) (400 µm)]. <b>h</b>, CRCs exhibiting strong cytoplasmic IQGAP3 staining (thick arrows) (400 µm). <b>i</b>, CRCs with lack of staining for IQGAP3 (thick arrows) (400 µm). <b>j</b>, NCE demonstrating moderate cytoplasmic staining of SLC6A8 staining (thin arrows) (600 µm). <b>k</b>, CRCs exhibiting strong cytoplasmic SLC6A8 staining with luminal accentuation (thick arrows) (600 µm). <b>l</b>, CRCs negative for SLC6A8 staining (thick arrows) (600 µm).</p

Cox regression analysis to determine prognostic significance of <i>p53</i> mutations.

1<p>Adjusted for the <i>p53</i> mutations, age, gender, tumor location, tumor grade, tumor size, tumor depth of invasion, nodal involvement, and adjuvant therapy.</p