Stathmin is an Independent Prognostic Marker of Poor Outcome in Uterine Leiomyosarcoma.

The objective of this study was to analyze the expression and prognostic role of cancer-associated proteins in uterine leiomyosarcoma (uLMS). p53, DAXX, ATRX, HMGA2, IMP3, Stathmin, and phospho-Stathmin (p-Stathmin) protein expression by immunohistochemistry was analyzed in tissue microarrays from 244 uLMS. Expression was assessed for association with clinicopathologic parameters in 173 patients with available data. Tissue microarrays were informative in 230 cases. p53 was aberrant in 44% of tumors. DAXX, ATRX, HMGA2, IMP3, and Stathmin were expressed in 90%, 55%, 40%, 33%, and 97% uLMS, respectively. Cytoplasmic and nuclear p-Stathmin staining was seen in 77% and 68% of tumors, respectively. Stathmin expression was significantly related to higher mitotic count (P < 0.001), a higher degree of atypia (P = 0.006), and vascular invasion (P = 0.016), whereas p-Stathmin expression was significantly related to advanced stage (P < 0.001), higher mitotic count (P < 0.001), and vascular invasion (P = 0.001). In univariate survival analysis for 165 patients with informative tissue microarrays, aberrant p53 (P = 0.026) and higher IMP3 (P = 0.024), Stathmin (P < 0.001), cytoplasmic p-Stathmin (P < 0.001), and nuclear p-Stathmin (P < 0.001) expression was associated with poor disease-specific survival. Clinicopathologic parameters significantly related to poor disease-specific survival were older age (P = 0.006), extrauterine disease at diagnosis (International Federation of Gynecology and Obstetrics (FIGO) stage ≥2; P < 0.001), high mitotic count (P = 0.02), and grade 2 to 3 atypia (P = 0.017). In multivariate analysis, age (P = 0.002), FIGO stage (P < 0.001), and Stathmin expression (P < 0.001) were independent prognosticators. Stathmin was the only prognosticator in a multivariate analysis limited to patients with FIGO stage I disease (P = 0.013). In conclusion, Stathmin expression is strongly associated with poor survival in uLMS and may be a new prognostic marker in this malignancy.

Tissue Factor Expression Does Not Predict Mortality in Breast Cancer Patients.

BACKGROUND: Tissue factor (TF), the trigger of coagulation, not only initiates thrombus formation, but also elicits tumor growth and invasion in breast cancer. However, the characterization of TF expression in breast cancer tissue and its prognostic value remain unclear. MATERIALS AND METHODS: Three hundred and three primary breast cancer specimens from the local tumor tissue database were immunostained for TF expression and evaluated semiquantitatively. Tumor characteristics (size, grade, nodal status, and ER expression) as well as patient's survival were assessed. RESULTS: Expression of TF was detected in 99% of specimens with higher expression in invasive lobular than ductal carcinoma (p=0.008). TF expression correlated with ER expression (p<0.0001) and inversely with tumor grade (p=0.006). Survival analysis did not reveal any prognostic impact of TF expression (p=0.966). CONCLUSION: This study - by analyzing TF expression in the largest cohort of breast cancer patients so far - does not support a prognostic impact of TF expression.

L1CAM protein expression is associated with poor prognosis in non-small cell lung cancer.

BACKGROUND: The L1 cell adhesion molecule (L1CAM) is potentially involved in epithelial-mesenchymal transition (EMT). EMT marker expression is of prognostic significance in non-small cell lung cancer (NSCLC). The relevance of L1CAM for NSCLC is unclear. We investigated the protein expression of L1CAM in a cohort of NSCLC patients. L1CAM protein expression was correlated with clinico-pathological parameters including survival and markers of epithelial-mesenchymal transition. RESULTS: L1CAM protein expression was found in 25% of squamous cell carcinomas and 24% of adenocarcinomas and correlated with blood vessel invasion and metastasis (p < 0.05). L1CAM was an independent predictor of survival in a multivariate analysis including pT, pN, and pM category, and tumor differentiation grade. L1CAM expression positively correlated with vimentin, beta-catenin, and slug, but inversely with E-cadherin (all p-values < 0.05). E-cadherin expression was higher in the tumor center than in the tumor periphery, whereas L1CAM and vimentin were expressed at the tumor-stroma interface. In L1CAM-negative A549 cells the L1CAM expression was upregulated and matrigel invasion was increased after stimulation with TGF-beta1. In L1CAM-positive SK-LU-1 and SK-LC-LL cells matrigel invasion was decreased after L1CAM siRNA knockdown. CONCLUSIONS: A subset of NSCLCs with vessel tropism and increased metastasis aberrantly expresses L1CAM. L1CAM is a novel prognostic marker for NSCLCs that is upregulated by EMT induction and appears to be instrumental for enhanced cell invasion.