Purpose: Aurora kinaseA (AURKA/STK15/BTAK) encodes a serine/threonine kinase associated with chromosomal distribution and its up-regulation induces chromosomal instability, thereby leading to aneuploidy and cell transformation in several types of cancer. In this study, we investigated the role of AURKA in head and neck squamous cell carcinoma (HNSCC). Experimental Design: The mRNA expression levels of AURKA were compared in tumor tissues of 66 HNSCC patients with those in corresponding normal squamous epithelium by real-time quantitative reverse transcriptase-PCR. In addition, the association between AURKA mRNA and protein expression, centrosome abnormalities, and aneuploidy was studied in a subset of cases (n = 34). All molecular variables were correlated to histomorphologic findings and clinical followup data of the patients. Results: AURKA mRNA up-regulation was significantly associated with tumor stage and the occurrence of regional lymph node, as well as distant metastasis (P < 0.0001 for all). Similarly, a correlation was found for protein expression and the occurrence of regional lymph node (P = 0.0183) and distant metastasis (P = 0.03).The mRNA was positively associated with protein expression (P = 0.003) and centrosome abnormalities (P = 0.03). Cox regression analysis revealed that AURKA mRNA up-regulation correlated with disease-free survival of the patients (P = 0.03) as well as shorter overall survival (P < 0.001). Conclusions:We conclude that the up-regulation of AURKA mRNA may play a critical role in the tumor progression of HNSCC and provides useful information as a prognostic factor for HNSCC patients.Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and survival rates are not improving (1). Therapeutic decisions are usually based on clinical and histopathologic variables like tumor-node-metastasis stage and tumor grading, which, however, often fail to predict patient outcome. Therefore, there is a need to better understand HNSCC development and progression on the molecular level. This should lead to an improved stratification between higherrisk and lower-risk patients, which can be treated in a more selective and individualized manner.DNA gains on chromosome 20q are recurrent findings in HNSCC (2, 3) and are associated with lymph node metastasis, as recently shown by array-based comparative genomic hybridization (4). Aurora kinase A (AURKA/BTAK/AIK1/ STK15) maps close to the critical region of this DNA gain and is localized on 20q13.2 (5). AURKA is a member of the Aurora/Ipl1p family of cell cycle -regulating serine/threonine kinases and is localized at interphase and mitotic centrosomes and at the spindle poles where it regulates proper chromosome segregation and cytokinesis (6). Recent studies have shown that the ectopic expression of Aurora-A in mouse NIH 3T3 cells and Rat-1 fibroblasts causes centrosome amplification and transformation in vitro as well as tumorigenesis in vivo (7,8). Furthermore, the up-regulation of AURKA leads to abnormal cent...

Proteomics-based approaches allow us to investigate the biology of cancer beyond genomic initiatives. We used histology-based matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry to identify proteins that predict disease outcome in gastric cancer after surgical resection. A total of 181 intestinal-type primary resected gastric cancer tissues from two independent patient cohorts were analyzed. Protein profiles of the discovery cohort (n ‫؍‬ 63) were directly obtained from tumor tissue sections by MALDI imaging. A seven-protein signature was associated with an unfavorable overall survival independent of major clinical covariates. The prognostic significance of three individual proteins identified (CRIP1, HNP-1, and S100-A6) was validated immunohistochemically on tissue microarrays of an independent validation cohort (n ‫؍‬ 118). Whereas HNP-1 and S100-A6 were found to further subdivide early-stage (Union Internationale Contre le Cancer [UICC]-I) and late-stage (UICC II and III) cancer patients into different prognostic groups, CRIP1, a protein previously unknown in gastric cancer, was confirmed as a novel and independent prognostic factor for all patients in the validation cohort. The protein pattern described here serves as a new independent indicator of patient survival complementing the previously known clinical parameters in terms of prognostic relevance. These results show that this tissue-based proteomic approach may provide clinically relevant information that might be beneficial in improving risk stratification for gastric cancer patients.

BACKGROUND: The aim of this study was to investigate the prognostic effect of tumour-infiltrating lymphocytes (TILs) in serous stage III ovarian carcinoma to determine TIL clonality and to correlate this to Her2/neu expression. METHODS: Formalin-fixed and paraffin-embedded ovarian carcinomas were examined for CD20-, CD3-, CD4-and CD8-positive lymphocytes (n ¼ 100), and for Her2/neu-positive tumour cells (n ¼ 55/100) by immunohistochemistry. Clonality analysis was carried out by T-cell receptor g (TCRg) gene rearrangements (n ¼ 93/100). Statistical analyses included experimental and clinico-pathological variables, as well as disease-free (DFS) and overall (OS) survival. RESULTS: CD20-positive B lymphocytes were present in 57.7% (stromal)/33.0% (intraepithelial) and CD3-positive T lymphocytes in 99.0% (stromal)/90.2% (intraepithelial) of ovarian carcinomas. Intraepithelial CD3-positive T lymphocytes were correlated with improved DFS in optimally debulked patients (P ¼ 0.0402). Intraepithelial CD8-positive T lymphocytes were correlated with improved OS in all optimally debulked patients (P ¼ 0.0201) and in those undergoing paclitaxel/carboplatin therapy (P ¼ 0.0092). Finally, rarified and clonal TCRg gene rearrangements were detected in 37 out of 93 (39.8%) and 15 out of 93 (16.1%) cases, respectively. This was marginally associated with improved DFS (P ¼ 0.0873). Despite a significant correlation of HER2/neu status and intraepithelial CD8-positive lymphocytes (P ¼ 0.0264), this was non-directional (R ¼ À0.257; P ¼ 0.0626). CONCLUSION: Improved survival of ovarian cancer patients is related to the infiltration, clonal selection and intraepithelial persistence of T lymphocytes.

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