The Study Of Phenomena Of Field Cancerization In Esophageal Squamous Cell Carcinoma

1. IntroductionEsophageal squamous cell carcinoma (ESCC) is one of the most commoncancers in China, with about 250 000 cases diagnosed every year. There are some specific behaviors in ESCC such as: ① multiple patches of pre-malignant lesions surrounding the main cancerous lesions, including mild dysplasia, moderate dysplasia, severe dysplasia ,cancer in situ.,and invasive cancer, etc.②often remain cancerous lesions after surgery of the primary tumor and may lead to new cancers, designated presently by clinicians as "a second primary tumor(SPT)" or "local recurrence," depending on the exact site and time interval. A higher-than-expected prevalence of multiple local SPTs.③The presence of synchronous and metachronous squamous cell carcinoma within the upper aerodigestive tract(UADT),for examples, cancer in oral cavity, tongue, larynx, trachea, bronchus and lung etc. ,and often develop second primary ESCC.The concept of "field cancerization" was first introduced by Slaughter[1] et al. in 1953 when studying the presence of histologically abnormal tissue surrounding oral squamous cell carcinoma. It was proposed to explain the development of multiple primary tumors and locally recurrent cancer. Organ systems in which field cancerization has been described since then are: headand neck (oral cavity, oropharynx, and larynx), lung, vulva, esophagus, cervix, breast, colon, bladder, and skin. However,there were not any precisely report in ESCC so far.2. Objective: ①To summary the clinical behaviers and therapeutics ofmultiple primary carcinoma(MPC) including synchronous or metachronous squamous cell carcinoma within the UADT. ② To investigate the clinic-pathological significance on the mucosal unstained areas with Lugol's iodine solution in the esophagectomy specimens of ESCC. ③To explore the TP53 protein expression at the multiple Lugol-voiding lesions out of the main cancerous lesions.④To comprehend the TP53 gene mutations in tissues of ESCC and the surounding mucosas.⑤To explore the clonality relationships from in the different lesions of ESCC and the surounding mucosas.3. Motheds: ①Reviewed the patients whom suffered from multipleprimary carcinoma(MPC),including synchronous or metachronous squamous cell carcinoma within the UADT those received surgical resection at Huaxi Hospital of Sichuan University from January, 2002 to April ,2005. ② Selected randomly forty-six(46) patients,32 male, 14 female, whom had been suffered from primary ESCC and undergone the esophagectomy in the department of Cardiothoracic Surgery , West China Hospital,Sichan University from February to May ,2004. Spraied 1.25% Lugol's iodine solution on the mucosas of the samples of esophagus in 2-5 minutes after esophagectomy. Took unstained areas in the mocosa of esophagus, and carried out routine staining with hematoxylin and eosin. And observed the clinic-pathological significance.③ Expression of TP53 protein byImmunohistochemistry(IHC) was performed using the ABC system on the unstained areas in the mocosa of esophagus of the 46 patients. In Negative controls were established by replacing the primary antibody with PBS. Esophageal cancerous tissue samples were obtained from 46 patients who received surgical resection at Huaxi Hospital of Sichuan University.④To set up a fast and sensitive test alternatives for TP53 gene defects in tissues, we analyzed ESCC by denaturing high performance liquid chromatography (DHPLC).4. Results: ①There were 28 cases with multiple primary cancinoma(MPCs)in esophagus and UADT in the whole 461 patients..The incidence rate were 6. 07 % (28/461) . There were 23 cases with synchronous MPC, including a case of combined with a squamous carcinoma of tongue and of multiple ones in esophagus. And 5 cases with metachronous carcinoma within the UADT. ②There were one hundred and thirty-two(132) unstained areas in the esophagus samples by Lugol's staining.Included Chronic esophagitis (31) ,mild dysplasia(21),moderate dysplasia(10),severe dysplasia(6),cancer in situ(5), early invasive carcinoma and advanced carcinoma(35),the incidence rate was 81.8% (108/132) .③The positive cancerous cells with p53 protein expression by IHC method were located in the nuclear,and closed to the basement membrane and cancer nests. There were 21 cases of positive in whole 46 cases in the group. The positive rate was 45.65% (21/46). And there were 15 cases of positive in 32 male cases. The positive rate was 46.9% (15/32). There were 6 cases of positive in 14 female cases. The positive rate was 42.9% (6/14). There were 12 cases with the mucosal multiple unstained areas by Lugol's iodine staining presented positive of p53 IHC staining inthose 21 cases also positive in main cancerous lesion. There were no significanal difference on gender, age, location , and stage of cancer.5. Conclusions:①There were a higher incidence rate of MPCs withinesophagus and UADT than the anticipated in the clinical experience. It should be more concerned. Esophagectomy and radiotherapy were the commonly used options in clinical so far. The etiology and therapeutic efficacy still need to be studied. The phenomena supported the concept of "field cancerization". ② There are the second site of carcinoma or/and precusors besides the major one in the patients from primary ESCC.The findings support the phenomena of "field carcinogenesis". ③The evidence of p53 protein expression support the concept of Field Cancerization in ESCC by IHC.④There were the phenomena of Field Cancerization in ESCC on TP53 gene mutation by DHPLC.