The prognostic significance of extramural deposits and extracapsular lymph node invasion in colon cancer.

BACKGROUND: The status of resected lymph nodes in colon cancer determines prognosis and further treatment. The American Joint Committee on Cancer staging system has designated extramural nodules as nonnodal disease and classified them as extensions of the T category in the sixth edition and as site-specific tumor deposits in the seventh edition. Extracapsular lymph node extension is an established poor prognostic indicator in many cancers. Its significance in colon cancer has not been extensively investigated. OBJECTIVE: This study aimed to determine the prognostic significance of extramural nodules and extracapsular lymph node extension in colon cancer. DESIGN: A pathological review of 114 stage III and 80 stage II colon cancers was undertaken to analyze for p-T stage, p-N stage (using the fifth, sixth, and seventh editions), and the size and contour of nodal and extramural deposits. Multivariate Cox regression models were used to determine the prognostic significance of clinicopathological parameters on survival estimates. RESULTS: According to the sixth and seventh editions of the guidelines, extramural deposits were present in 29% and 31% of patients with stage III colon cancer and in 5% of patients with stage II colon cancer. Extracapsular lymph node invasion was present in 68% of cases. Multivariate analysis demonstrated that lymph node ratio, extracapsular lymph node extension, and adjuvant chemotherapy were independent prognostic factors affecting 5-year disease-free survival. The same 3 variables, in addition to extramural deposits, were independent prognostic factors affecting overall survival. The presence of extramural deposits was associated with an 11% 5-year survival, and extracapsular lymph node invasion was associated with a 33% 5-year survival. CONCLUSIONS: Instead of extramural nodules being included as part of the T category or as site-specific tumor deposits, they should perhaps be classified in the metastasis category. This has major prognostic implications and may broaden the application of a number of adjuvant agents.

Surgical injury enhances the expression of genes that mediate breast cancer metastasis to the lung.

OBJECTIVE: This study was conducted to test the hypothesis that surgery induces changes at the expression level of genes implicated in metastasis, thus leading to accelerated postoperative metastatic tumor growth. SUMMARY BACKGROUND DATA: Surgical resection of the primary tumor is a necessary and effective treatment for breast cancer patients. However, studies from both animals and humans have shown that surgery potentiates the growth of minimal residual neoplastic disease. METHODS: : Female BALB/c mice were inoculated with metastatic murine mammary adenocarcinoma 4T1-green fluorescent protein (GFP) cells in the mammary fat pad (3 × 105/mouse), and divided into a surgery group (n = 12) in which the flank tumor was completely resected after 21 day growth and a control (no surgery) group (n = 12). Metastatic tumor burden was assessed by both macroscopic metastatic nodule count and clonogenic assay. Mitotic and apoptotic indices were established using a combination of hematoxylin-eosin histology and Ki-67 immunohistochemistry. Green fluorescent protein (GFP) expressing tumor cells were isolated using FACS sorting, and RNA was extracted. The RT² Profiler PCR Array mouse Cancer Pathway Finder was used to determine and compare the mRNA levels of 84 genes involved in metastasis in both groups. RESULTS: Excision of the primary tumor was associated with increased systemic metastatic burden (P = 0.001). Postoperative metastases exhibited increased proliferation (P = 0.001), but no reduction in apoptosis. The quantitative real-time polymerase chain reaction array data indicate that surgery significantly upregulated the expression of Itgb3, Egfr, Hgf, Igf1, Pdgfb, Tnfα, Vegfa, Vegfc, and MMP9 genes, and led to the down regulation of Cdkn2a, Cdh1, and Syk genes. Increased expression of ITGB3 and MMP9 was further confirmed at the protein level by Western blot. CONCLUSIONS: Removal of the primary tumor led to a progressive phenotype of lung metastases that exhibited upregulation of genes involved in adhesion, invasion, and angiogenesis.

Identification of two molecular groups of seminomas by using expression and tissue microarrays.

Highly effective tailored clinical management of testicular germ cell tumors is based on the identification of two major histologic subtypes: seminomatous and nonseminomatous germ cell tumors. Expression array analysis of these two histologic subtypes using hierarchical clustering reveals two tumor groups, one composed solely of seminomas and the other containing embryonal carcinomas and seminomas. Supervised analysis between these groups identified 55 significantly dysregulated genes (false discovery rate = 2.3). The genes with the highest overexpression in the first group compared with the second included SLC43A1 (POV1), NET-7, IGF2, and JUP; down-regulated genes included GRB7, PFKP, and CDC6. In situ hybridization of SLC43A1 mRNA showed significantly increased signal intensity in the seminomas. At the protein level, expression of the immunohistochemical markers cytokeratins (pan-cytokeratin staining), placental-like alkaline phosphatase, anti-cytokeratin clone 5.2, CD30, anion exchanger 1/3, junction plakoglobulin (JUP), and POU domain, class 5, transcription factor 1 (octomer-binding transcription factor 3/4) was significantly different between seminomas and embryonal tumors. Hierarchical clustering based on a refined protein expression profile identified two groups, the first consisting solely of seminomas the other of seminomas and embryonal carcinomas. No histomorphologic differences were observed between the two seminoma groups such as the presence or absence of lymphocytes or extent of stromal elements. In summary, using independent methodologies and samples, we have identified two groups of seminomas. One group of seminomas has a molecular profile similar to embryonal carcinoma. The findings in the current study may help explain aberrant immunoprofiles seen with some seminomas.