Pathological study of non-neoplastic skin lesions by punch biopsy

Background: Accurate diagnosis of skin disorders is of utmost importance as treatment is varied for different skin disorders presenting with the similar clinical lesions. Thus biopsy becomes inevitable in various skin disorders to confirm diagnosis and initiate treatment. The present study was to analyse the age and sex distribution of dermatological disorders presenting to Bhaskar Medical College & Hospital (tertiary care centre), Telangana and assess their histo-pathological profile. The objective was to analyse the histo-pathological profile of skin disorders presenting to the Dermatology department of the hospital, determine the age and sex distribution of various skin diseases and to classify the most common disorders into their subtypes and thus assess the most common subtypes prevalent in the surrounding community.Methods: This was a prospective study carried out at the department of Pathology and department of Dermatology, Bhaskar Medical College & Hospital for a period of three years. Necessary clinical details were obtained in a proforma, punch biopsy taken and sent to the histopathology section for final report. Formalin fixed, paraffin embedded sections were prepared & slides were routinely stained with H & E and special stains applied wherever necessary. Data obtained was tabulated and analysed.Results: Total number of cases analysed were 92. The age group of 21-30 years constituted 31.5% of the total cases. There was a male predominance. Hyperpigmented patch/plaque was the most common clinical lesion (36.9%). Lichenoid lesions was the most common histopathological diagnosis reported (26%) followed by Hansen’s disease(23.9%). Lichen planus was the most common histopathological subtype of lichenoid lesion s(58.3%).

Significance of differential expression of thymidylate synthase in normal and primary tumor tissues from patients with colorectal cancer

The role of thymidylate synthase (TS) is essential as a key rate-limiting enzyme in DNA synthesis. It is the primary target of fluorouracil and its derivates in colorectal cancer. In this study, TS mRNA expression was examined in primary tumor and normal tissues from 76 patients with high- risk stage II/III colorectal cancer by laser capture microdissection and polymerase chain reaction. Thirty (39.47%) patients were found to have higher TS expression in primary tumors with earlier stage (P = 0.018), lower histological grades (P = 0.001) and high frequency microsatellite instability (P = 0.000). Multivariate analysis showed that microsatellite instability, histological grade and number of lymph nodes examined are independent prognostic markers

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

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

Immunophenotypic profiles and prognosis for colorectal mucinous adenocarcinomas are dependent on anatomic location

Abstract Background The prognostic value of mucinous adenocarcinomas (MCAs, exhibiting >50% extracellular mucin) of the colorectum, in relation to their anatomic location is not well studied. Materials and Methods We compared MCAs (n = 175) with non‐MCAs (NMCAs, n = 1015) and the cancer‐specific survival rates were evaluated, based on their anatomic site, by univariate Kaplan–Meier and multivariate Cox methods. Subsets of these tumors were immunostained for MUC1, MUC2, Bcl‐2, and p53. Results MCAs were more commonly found in the right colon, were of high‐grade, and were more prevalent in younger patients (<40 years). They exhibited strong expression of MUC2 and Bcl‐2 and showed less p53 nuclear staining. In contrast, most NMCAs were low‐grade with high expression of MUC1. MCAs of the rectum were associated with poorer outcomes relative to NMCAs (HR 1.85, CI 95% 1.15–2.97), even though the distributions of advanced‐stage tumors were similar. Conclusion Late‐stage disease and age were poor independent prognostic indicators of cancer‐specific deaths across all tumor locations. In summary, rectal MCAs have a poor prognosis

The combined survival effect of codon 72 polymorphisms and p53 somatic mutations in breast cancer depends on race and molecular subtype.

BackgroundThe codon 72 polymorphism in the p53 gene relates to the risk of breast cancer (BC), but this relationship in racially diverse populations is not known. The present study examined the prognostic value of this polymorphism for African American (AA) and Caucasian (CA) BC patients separately and considered the confounding variables of molecular subtypes and somatic mutations in p53.MethodsTissue sections of BCs from 116 AAs and 160 CAs were evaluated for p53 mutations and genotyped for the codon 72 polymorphism. The relationships of phenotypes to clinicopathologic features were determined by χ2 analyses; patient survival was estimated by Kaplan-Meier univariate and Cox regression multivariate models in a retrospective cohort study design.ResultsThe proportion of single nucleotide polymorphism (SNP) 72 alleles differed for races. Many cancers of AAs were Pro/Pro, but most for CAs were Arg/Arg. A higher frequency of missense p53 mutations was evident for AAs. There was an interaction between the SNP allele and p53 mutations for AA women only. The proportion of women with both the Pro/Pro allele and a p53 somatic mutation was higher for AA than CA women. The interaction between missense p53 mutations and Pro/Pro had a negative effect on survival, particularly for AAs with luminal cancers.ConclusionsFor BCs, the survival effect of SNP72 combined with a p53 missense mutation is dependent on race and molecular subtype. Although such a mutation is a marker of poor prognosis, it is relevant to identify the variant Pro/Pro in the case of AAs, especially those with luminal subtypes of BC

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

The prognostic significance of <i>p53</i> mutations in survival of Stage III CRC patients with MSS or MSI-H phenotypes (Kaplan-Meier survival curves).

<p><i>p53</i> mutations were associated with worse patient survival (log-rank, <i>P</i> = 0.025) (<b>A</b>) than wt-<i>p53</i> in the subset of MSS phenotype, but not in the subset of MSI-H phenotype (log-rank, <i>P</i> = 0.695) (<b>B</b>).</p