In this study, we examined a large number of patients to clarify FLT3 gene has some structural similarities including the the distribution and frequency of a recently described FLT3 tannumber of exons, size of exons and exon/intron boundaries dem duplication among hematopoietic malignancies, including with genes RTKs, FMS, KIT, and platelet-derived growth-factor of 24 showed internal tandem duplication with or withoutWe recently demonstrated internal tandem duplication insertion of nucleotides. In one AML, insertion and deletion within JM/TK-I domains as a somatic mutation of FLT3 found without duplication was determined. All 24 lengthened in 17% of patients with acute myelogenous leukemia (AML). 14 sequences were in-frame. Duplication takes place in the Since this mutation was not found in any patients with acute sequence coding for the JM domain and leaves the TK domain lymphocytic leukemia, we described that this mutation could intact. In conclusion, we emphasize that the length mutation of FLT3 at JM/TK-I domains were restricted to AML and MDS.be specific in myeloid malignancies. To clarify the incidence Since all these mutations resulted in in-frame, this abnormality and distribution of the FLT3 mutation among hematological might function for the proliferation of leukemic cells.malignancies, we examined a large number of patients with

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These results indicate that postoperative infectious complications may worsen patient prognosis after esophagectomy. Performing esophagectomy without postoperative complications, especially pneumonia, may be beneficial for improving survival outcomes.

Summary Our recent analysis of gastric cancers using comparative genomic hybridization (CGH) revealed a novel high frequent copy number increase in the long arm of chromosome 20. Tumour-amplified kinase BTAK was recently cloned from breast cancers and mapped on 20q13 as a target gene for this amplification in human breast cancers. In the study presented here, we analysed BTAK copy-number and expression, and their relation to the ploidy pattern in 72 primary gastric cancers. Furthermore, wild-type BTAK and its deletion mutants were transfected to gastric cancers to examine changes in cell proliferation and DNA ploidy pattern. Evaluation of 72 unselected primary gastric cancers found BTAK amplification in 5% and overexpression in more than 50%. All four clinical samples with BTAK amplification showed aneuploidy and poor prognosis. Transfection of BTAK in near-diploid gastric cancers induced another aneuploid cell population. In contrast, the c-terminal-deleted mutant of BTAK induced no effect in DNA ploidy pattern and inhibited gastric cancer cell proliferation. These results suggest that BTAK may be involved in gastric cancer cell aneuploid formation, and is a candidate gene for the increase in the number of copies of the 20q, and thus may contribute to an increase in the malignant phenotype of gastric cancer.

238 Background: Neoadjuvant treatment is the standard care for locally advanced esophageal squamous cell cancer (ESCC). JCOG1109 (UMIN000009482) compared the doublet and triplet of chemotherapy and chemoradiotherapy as neoadjuvant treatment. Methods: Eligible patients (pts) with ESCC of clinical stage IB, II, III (excluding T4) (UICC 7th) from 44 institutions were randomized 1:1:1 to neoadjuvant CF (cisplatin 80 mg/m2 on day1 plus 5-FU 800 mg/m2 on days 1-5 Q3W/2course), DCF (docetaxel 70 mg/m2 on day 1, cisplatin 70 mg/m2 on day1, plus 5-FU 750 mg/m2 on days 1-5 Q3W/3 course), or CF-RT (cisplatin 75 mg/m2 on day 1 plus 5-FU 1000 mg/m2 on days 1-4 Q4W/2course, radiation 41.4 Gy/23 fr). Primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), %R0 resection, %objective response by neoadjuvant therapy, %pathological complete response (pCR) and safety. Differences in OS was assessed in the ITT using the stratified log-rank test. The data cutoff date for the analysis was July 20, 2021. Results: Of 601 pts 199 CF, 202 DCF, and 200 CF-RT were enrolled from December 5, 2012 to July 20, 2018, respectively. Among 601 pts, 88.2% were male, median (range) age was 65 (30-75), clinical stage III (nonT4) pts were 62.6%. Median follow-up time (range) was 4.2 years (y) (0-8.5). Median OS in CF, DCF, and CF-RT arm were 4.6 y, not reached (NR), and 6.0y, and 3-year OS was 62.6%, 72.1%, and 68.3%, respectively (stratified log-rank test: p = 0.006 for CF vs. DCF and p = 0.12 for CF vs. CF-RT). By stratified Cox regression analysis for OS, hazard ratios (HR) [95% CI] was 0.68 [0.50–0.92] for CF vs. DCF and 0.84 [0.63–1.12] for CF vs. CF-RT. Median PFS in CF, DCF, and CF-RT arm were 2.7 y, NR, and 5.3 y, and 3-year PFS was 47.7%, 61.8%, and 58.5%, respectively. R0 resection was achieved in 168 (84.4%), 173 (85.6%), and 175 (87.5%), and pCR was 4 (2.1%), 40 (19.8%), and 77 (38.5%), respectively. During neoadjuvant therapy, febrile neutropenia in CF, DCF, and CF-RT arm were 1.0%, 16.3% and 4.7%, and esophagitis (grade>3) were 1.0%, 1.0% and 8.9%, respectively. The treatment-related death was seen in 3 (1.5%), 4 (2.0%), and 2 (1.0%), in CF, DCF, and CF-RT arm, respectively. Conclusions: DCF significantly improved OS over CF as neoadjuvant therapy for locally advanced ESCC, with a manageable toxicity profile. DCF represents a new standard neoadjuvant treatment for ESCC. Clinical trial information: UMIN000009482.