Chin J Lung Cancer February 2006 Vol. 9 No ErbB1[ EGFR (epidermal growt h fac2 tor receptor ) H ER1 ] ErbB2 ( H ER2 ) ErbB3 ( H ER3)

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1 Chin J Lung Cancer February 2006 Vol. 9 No. 1 DOI: /j.issn H ER2 H ER2 80 H ER H ER %(23/ 74) H ER % %( P = ) H ER2 ( P = ) H ER2 H ER2 H ER2 H ER2 R Tissue microarray analysis of HER2 protein expression in patients with non2small cell lung cancer L I N ing W A N G B o Z HA N G X ing PA N Zhenkui X U Fei W A N G Zhiqiang Z HA N G Yang Z HA N G L i. Can2 cer Center of S un Yat2S un Universit y S tate Key L aboratory of Oncolog y in S outhern China Guangz hou Guang dong P. R. China Corres ponding author : Z HA N G L i E2mail : z edu. cn Abstract Background and objective Tissue microarray provides a high throughput tool for protein analysis. The aim of this study is to test the expression of H ER2 protein in non2small cell lung cancer ( NSCL C) by tissue microarray and analyze the relationship between H ER2 protein expression and chemother2 apeutic response rate and survival. Methods Using tissue microarray H ER2 protein expression was detected in patients with advanced NSCL C by immunohistochemistry. Results Total 80 patients were enrolled in the study. Only 74 patient s could be reviewed for H ER2 staining. The response rate to chemotherapy in positive and negative H ER2 expression group s was % and % respectively ( P = ). The survival differ2 ence was also not significant between the positive and negative H ER2 protein expression groups ( P = ). Conclusion The combination of tissue microarray and immunohistochemistry represents a highly feasible tech2 nique for examination of H ER2 protein expression in NSCL C. There is no significant difference in survival be2 tween positive and negative H ER2 expression groups. The role of H ER2 protein in NSCLC should be further studied. Key words Non2small cell lung cancer H ER2 Tissue microarray This work was supported by a grant f rom Science and Technology Foundation of Guangdong Province (to ZHAN G Li) (No. 2004B ). (tissue microarray) 0. 6 mm (2004B ) : ( : E2mail edu. cn) [1 ] ( ErbB )

2 Chin J Lung Cancer February 2006 Vol. 9 No ErbB1[ EGFR (epidermal growt h fac2 tor receptor ) H ER1 ] ErbB2 ( H ER2 ) ErbB3 ( H ER3) ErbB4 ( H ER4) [2 ] H ER2 185 ku H ER2 17 H ER (epidermal growt h factor EGF) [3 ] H ER2 [4 ] H ER2 trast u2 zumab ( Herceptin g ) ( Food and Drug Administration FDA ) H ER22 ( no n2small cell lung cancer NSCL C) H ER2 Tsai [5 ] RNA ( Northern blot) NSCL C H ER22/ neu mrna 1. 3 H ER2 Bunn [6 ] H ER22/ neu NSCL C 3 % H2 O2 10 min PBS ( trast uzumab p H7. 2) (p H6. 0) 15 min PBS H ER2 (1 100) (DA KO ) min (DA KO) NSCL C H ER min 30 min PBS DAB 1 FDA H ER B/ NSCL C 80 0 : ;1 + :10 % 1 ; 2 + : 10 % ; : 10 % (1) ( 1. 0 g/ m ; mg/ m ) 65 H ER H ER2 2 + ( 80 mg/ m H ER mg/ m mg/ m mg/ m SPSS10. 0 ) CT 4 2 H ER2 Kaplan2Meier P < H E mm 5 mm (92. 5 %) H ER2 4m 1 80 NSCLC Tab 1 Pathological characteristics of 80 NSCLC patients Characteristic Age (year) Median 55 Range Sex Male 47 Female 33 Histology Squamous cell carcinoma 25 Adenocarcinoma 55 TNM staging B Regimen Gemcitabine + vinorelbine 15 Gemcitabine + cisplatin 46 Paclitaxel + cisplatin 14 Vinorelbine + cisplatin 5 NSCL C H ER ; n

3 Chin J Lung Cancer February 2006 Vol. 9 No ; ; B % (36. 0 %) ;62 ( % ) CT 4 (2) H ER2 TNM (time to progression T TP) (progression2free survival PFS) ( P = H ER2 NSCL C 23 H ER ) (3 2) 1 HER2 (40 ) A :0 HER2 ;B : % ;C : % ;D : % Fig 1 HER2 protein expression in NSCLC patient s on a tissue microarray (40 ) A : Score 0 : Negative staining for HER2 ; B : Score 1 + : Weak membranous staining in less t han 10 % of tumor cells ; C : Score 2 + : Moderate mem2 branous staining in more t han 10 % of tumor cells : D : Score 3 + : Strong membranous staining in more t han 10 % of tumor cells 2 74 H ER2 Tab 2 Expression of H ER2 protein in different histopathologic type of 74 patients Histology 0 ( %) 1 + ( %) 2 + ( %) 3 + ( %) L ( %) H ( %) Squamous cell carcinoma 11 (45. 8) 8 (33. 3) 4 (16. 7) 1 (4. 2) 19 (79. 2) 5 (20. 8) Adenocarcinoma 22 (44. 0) 10 (20. 0) 10 (20. 0) 8 (16. 0) 32 (64. 0) 18 (36. 0) P value L : Low including score of 0 and 1 + ; H : High including score of 2 + and H ER2 TNM TTP PFS Tab 3 Relationship between H ER2 protein expression and TNM stage TTP PFS and response rate HER2 protein expression B TNM stage T TP (mont h) Mean 95 % CI PFS (month) Mean 95 % CI Response rate Positive expression / 23 (39. 1 %) Negative expression / 51 (51. 0 %) P value

4 Chin J Lung Cancer February 2006 Vol. 9 No HER2 Fig 2 Comparison of survival duration between patient s wit h positive and negative HER2 protein expression 3 H ER2 Kononen EGFR [ ] EGFR NSCL C H ER2 [8 ] 80 NSCL C trastuzumab 74 H ER2 NSCL C H ER2 NSCL C 27 %57 [9 % ] H ER2 NSCL C 1255 H ER2 : H ER2 H ER2 mary laryngeal carcinoma by the tissuechip technology. Chin J [10 ] H ER2 [11 ] Tsai [5 ] NSCL C H ER2 H ER2 Yu [12 ] H ER2 H ER2 trast uzumab NSCL C ECO G( ) 2598 t rast uzumab 56 NSCL C % % H ER [13 ] + trastuzumab + [14 ] H ER % H ER2 H ER2 TNM T TP PFS H ER2 H ER2 H ER H ER2 15 H ER2 15 H ER2 1 Jin B Zhu J C Dong P et al. Research of fibronectin p53 and Ezrin protein with occurrence progress and prognosis in the pri2 Otorhinolaryngol ( 11) [. p53 Ezrin (11) ] 2 Onn A Correa AM Gilcrease M et al. Synchronous overexpres2 sion of epidermal growth factor receptor and HER22neu protein is a predictor of poor outcome in patient s wit h stage non2small cell lung cancer. Clin Cancer Res (1 Pt 1) Hirsch FR Franklin WA Veve R et al. HER2/ neu expression in malignant lung tumors. Semin Oncol (1 Suppl 4) Nakamura H Saji H Ogata A et al. Correlation between enco2 ded protein overexpression and copy number of the HER2 gene with survival in non2small cell lung cancer. Int J Cancer (1) Tsai CM Chang KT Wu L H et al. Correlations between intrin2 sic chemoresistance and HER22/ neu gene expression p53 gene mutations and cell proliferation characteristics in non2small cell lung cancer cell lines. Cancer Res (1) Bunn PA J r Helfrich B Soriano AF et al. Expression of Her22/

5 Chin J Lung Cancer February 2006 Vol. 9 No. 1 neu in human lung cancer cell lines by immunohistochemistry and fluorescence in situ hybridization and its relationship to in vit ro cy2 totoxicity by trastuzumab and chemotherapeutic agents. Clin Can2 cer Res (10) Jin C Chen SQ Lin M et al. Application of high2t hroughput tis2 sue microarray technique on p53 protein expression in nasopharyn2 geal carcinoma. Chin J Cancer Prev Treat (8) [. p53 tion of metastasis2associated properties. Cancer Res (8) ] 8 Zhang RS Meng K Shi QL et al. Application of tissue microar2 ray technique on specially positive staining. Chin J Clin Exp Pat hol (4) [.. ern Cooperative Oncology Group study J Clin Oncol (4) ] 9 Bratt strom D Wester K Bergqvist M et al. HER22 EGFR COX22 expression status correlated to microvessel density and sur2 vival in resected non2small cell lung cancer. Acta Oncol (1) Meert AP Martin B Paesmans M et al. The role of HER22/ neu expression on the survival of patients with lung cancer : a system2 atic review of t he literature. Br J Cancer (6) Pollan M Varela G Torres A et al. Clinical value of p53 c2 erbb22 CEA and CA125 regarding relapse metastasis and death in resectable non2small cell lung cancer. Int J Cancer (5) Yu D Wang SS Dulski KM et al. c2erbb22/ neu overexpression enhances metastatic potential of human lung cancer cells by induc2 (12) Langer CJ Stephenson P Thor A et al ; Eastern Cooperative On2 cology Group Study Trastuzumab in the treatment of ad2 vanced non2small2cell lung cancer : is t here a role? Focus on East2 (7) Rosell R. Toward customized trastuzumab in HER22/ neu2overex2 pressing non2small2cell lung cancers. J Clin Oncol (7) ( : : ) () R ;R : ; T2 N0 M1 ; T1 N0 M0 A ; CT mm B PET 12 : Martini [1 ] 1 Martini N Melamed MR. Multiple primary lung cancers. J Thorac Cardiovasc Surg % % [2 ] (4) Duchateau CS Stokkel MP. Second primary : 3. 5 cm tumors involving non2small cell lung cancer : ; 3. 5 cm 3. 0 cm prevalence and it s influence on survival cm 1. 5 cm 1. 0 cm Chest (4) ; / 3 Braakhuis BJ Tabor MP Kummer J A et 0. 8 cm 0. 8 cm ; al. A genetic explanation of Slaughter s con2 cept of field cancerization : evidence and clin2 : [3 ] ical implications. Cancer Res (8) ( ( : : ) ) ( : E2mail mail. sc. cninfo. net) CT ()

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<4D6963726F736F667420576F7264202D20B2CCA3BA4542B2A1B6BE52746120496747BFB9CCE5D3EBB1C7D1CAB0A9B7D6C6DAB5C4B9D8CFB52E646F63> EB 病毒 Rta/IgG 抗体与鼻咽癌分期的关系蔡永林, 郑裕明, 成积儒, 李军, 莫永坤, 钟青燕 ( 广西梧州市红十字会医院, 梧州市肿瘤防治研究所, 广西梧州 543002) 摘要 : 目的探讨 EB 病毒 Rta/IgG 抗体与鼻咽癌临床分期的关系方法用酶