Background: HAX-1 has been described as a protein potentially involved in carcinogenesis and especially metastasis. Its involvement in regulation of apoptosis and cell migration along with some data indicating its overexpression in cancer cell lines and tumors suggests that HAX-1 may play a role in neoplastic transformation. Here we present the first systematic analysis of HAX-1 expression in several solid tumors.Methods: Using quantitative RT-PCR, we have determined the mRNA levels ofHAX1splice variant I in several solid tumors. We have also analyzed by semiquantitative and quantitative RT-PCR the expression of fiveHAX-1splice variants in breast cancer samples and in normal tissue from the same individuals. Quantitative PCR was also employed to analyze the effect of estrogen onHAX1expression in breast cancer cell line. Immunohistochemical analysis of HAX-1 was performed on normal and breast cancer samples.Results: The results reveal statistically importantHAX1up-regulation in breast cancer, lung cancer and melanoma, along with some minor variations in the splicing pattern. HAX-1 up-regulation in breast cancer samples was confirmed by immunohistochemical analysis, which also revealed an intriguing HAX-1 localization in the nuclei of the tumor cells, associated with strong ER status.Conclusion: HAX-1 elevated levels in cancer tissues point to its involvement in neoplastic transformation, especially in breast cancer. The connection between HAX-1 nuclear location and ER status in breast cancer samples remains to be clarified.

BACKGROUND: The objectives of the current study were to assess the reliability of the new revision of the American Joint Committee on Cancer (AJCC) staging system for gastrointestinal stromal tumors (GISTs) based on the National Comprehensive Cancer Network‐Armed Forces Institute of Pathology risk classification and to analyze the factors that influence after resection for primary GISTs in 2 AJCC groups: patients with GISTs originating from the stomach and omentum (G‐GISTs) and patients with other primary GISTs located mainly in the small bowel (nongastric GISTs [NG‐GISTs]).METHODS: The authors prospectively analyzed a group of 640 patients with primary, CD117‐positive GISTs who underwent surgery with curative intention (R0/R1 resection), including 340 G‐GISTs (55.5%) and 300 NG‐GISTs (44.5%). Factors were explored that had an effect on disease‐free survival time (DFS), which was calculated from the date of radical operation to the date of recurrence or last follow‐up. The median follow‐up was 39 months.RESULTS: Compared with NG‐GISTs, G‐GISTs were characterized by a significantly lower median size (5.3 cm and 8.5 cm, respectively; P < .0001) and lower mitotic activity (median, 3 in 50 high‐power fields [HPF] vs 5 in 50 HPF; P < .0001), and they were diagnosed in older patients (median age, 62 years vs 57 years; P = .002). The most commonly detected mutations in G‐GIST were those located in KIT exon 11 (60.5%) and platelet‐derived growth factor receptor alpha (PDGFRA) exon 18 (19%) versus KIT exons 11 and 9 in NG‐GISTs (72% and 17.4%, respectively). The prognosis of patients who had G‐GISTs was significantly better compared that of patients who had NG‐GISTs, with 5‐year DFS rates of 69% (median, 83 months) versus 43% (median, 33 months), respectively (P < .00001). The most significant prognostic factors that correlated with shorter DFS in both G‐GISTs and NG‐GISTs were primary tumor size >5 cm and >10 cm (P < .0001) and mitotic index >5 in 50 HPF and >10 in 50 HPF (P < .0001). The 5‐year DFS rates in G‐GISTs according to AJCC stage categories were as follows: 96% for stage IA tumors, 92% for stage IB tumors, 51% for II tumors, 22% for stage IIIA tumors, and 22% for stage IIIB tumors (P < .0001). The 5‐year DFS rates in NG‐GISTs according to AJCC categories were as follows: 92% for stage I tumors, 66% for stage II tumors, 28% for IIIA tumors, and 16% for IIIB tumors (P < .0001). The high prognostic significance of the AJCC classification also was confirmed for overall survival data, including the impact of therapy with tyrosine kinase inhibitors.CONCLUSIONS: The reliability of AJCC risk classification after resection of primary GIST was confirmed for DFS and overall survival. Patients with primary G‐GISTs had a better prognosis than patients with NG‐GISTs. In both groups, primary tumor size and mitotic activity were the most important prognostic factors in terms of DFS. Cancer 2011;. © 2011 American Cancer Society.