Apoptotic and proliferative indexes in esophageal cancer: predictors of response to neoadjuvant therapy [corrected].

Altered expression of the genes that control apoptosis and proliferation may influence the response of cancer cells to cytotoxic agents. The primary aim of this study was to determine the role of the novel antiapoptotic and cell cycle gene, survivin, in apoptotsis and proliferation in esophageal cancer and to evaluate whether the survivin, p53, and bcl-2 status were able to predict a patient's response to neoadjuvant therapy. A total of 104 patients with esophageal tumors were studied. Tumor tissue was immunostained for survivin, p53, and bcl-2 proteins. Proliferative and apoptotic activity was measured using ki-67 immunohistochemical analysis and the TUNEL method, respectively. Forty-eight patients whose pretreatment biopsies were analyzed received neoadjuvant chemoradiation therapy or chemotherapy followed by surgery. Outcome was graded as a complete response, a partial response, or no response according to the results of histologic examination and CT imaging. Expression of survivin was found to correlate significantly with the proliferative index but not the apoptotic index. Patients who received neoadjuvant treatment were more likely to achieve a complete response if their tumors had high proliferative activity, and p53 positive tumors were more likely to contain residual tumor after treatment. In conclusion, survivin expression appears to foster proliferative activity in esophageal cancer, and tumors with a high proliferative index or a functioning p53 gene are more responsive to neoadjuvant chemoradiation therapy.     

乳腺癌p53，ki-67和bcl-2的表达与新辅助化疗的关系

目的 研究乳腺癌p53,ki-67和bcl-2基因蛋白表达与新辅助化疗临床效果的关系,以寻找指导治疗、判断预后的生物学指标.方法 采用免疫组化SABC法测定118例可手术的乳腺癌标本的p53,ki-67和bcl-2的蛋白表达,并分析其与新辅助化疗疗效的关系.结果 术前辅助化疗有效率为68.6%.p5 3表达阳性,化疗效果差（P＜0.05）;而ki-67阳性表达者有效率明显高于ki-67不表达者（P＜0.05）;bcl-2表达与疗效无明显关系.p53蛋白阳性表达者bcl-2表达下降.p53与ki-67蛋白表达有明显关系.结论 p53和ki-67蛋白表达可作为指导新辅助化疗及预后判断的分子生物学指标.     

Early response evaluation and prediction in neoadjuvant-treated patients with esophageal cancer

Since the introduction of multimodal therapy regimens, the prognosis of esophageal cancer has improved. There is undoubtedly true for patients with surgically resected tumors in the case of a response to neoadjuvant chemotherapy or chemoradiation. Important conclusions can be drawn from this regarding the indication for perioperative therapies, the radicality of surgery, or the surgical indications. Thus, most of the current research in this field is aimed at the early identification of this subset of patients, at the beginning of, or even before, neoadjuvant treatment. Conventional staging tools have failed to predict responses to neoadjuvant therapy. However, molecular imaging methods, e.g. positron emission tomography (PET)-scans, have shown promising results in the early selection of responders and non-responders during the course of neoadjuvant therapy, allowing physicians to alter the treatment plan accordingly. Even more desirable is the identification of potential responders before the start of neoadjuvant therapy. Preliminary molecular data on biopsy specimens demonstrate the possibility of early response prediction in these patients. We present the current knowledge on response evaluation and prediction in esophageal cancer and draw conclusions for future clinical practice and studies in this review.     

Multimodality treatment of esophageal cancer

Stage specific management of non-small cell lung cancer is widely accepted. The use of pretreatment disease stage to guide therapy for esophageal cancer is an intellectually appealing concept. To date, there isa relative lack of data upon which one may base stage specific treatment decisions for esophageal carcinoma. This is because thorough pretreatment TNM staging is not universally practiced. As a result, stage-specific treatment varies widely. Based upon the available data, surgery alone may be appropriate for resectable, node-negative disease. In the case of clearly un-resectable disease, definitive chemoradiation is indicated.The value of neoadjuvant or adjuvant treatment modalities in the case of clearly resectable node-negative disease (TlN0 or T2N0) is questionable;however, in the presence of lymph node involvement (N1), or in the case of a marginally resectable primary tumor (T3 or T4), neoadjuvant chemoradiation is probably indicated. Although the achievement ofa complete pathologic response following chemoradiation may obviate surgical resection, even microscopic residual cancer can result in local recurrence. To date, there is no reliable method of ascertaining a complete pathologic response before surgical resection. Therefore, when feasible, the addition of surgical resection following chemoradiation is warranted.Future treatment trials for esophageal cancer should include rigorous pretreatment staging protocols to elucidate stage-specific results of therapy.     

Multimodality treatment for esophageal cancer: the role of surgery and neoadjuvant therapy

Treatment of esophageal cancer has traditionally included surgery as the initial modality. Neoadjuvant chemoradiation therapy has been introduced with the goal of downstaging tumors before surgical resection; however, its role in esophageal cancer remains controversial. We report 116 patients who underwent esophagogastrectomy with reconstruction for carcinoma of the esophagus or esophagogastric junction over a 10-year period (January 1, 1990 to June 1, 2001). Forty patients underwent neoadjuvant radiation and chemotherapy followed by surgery. Hospital mortality in this group was 7.5 per cent, complete pathologic response (CPR) was 37.5 per cent, and overall 3- and 5-year survival rates were 47 and 38 per cent. Five-year survival in the 15 patients with CPR was 85 per cent. Five patients underwent neoadjuvant single-agent therapy (four chemotherapy and one radiation) followed by surgery, and none survived to 3 years. Seventy-one patients underwent surgery without neoadjuvant therapy. Hospital mortality in this group was 1.4 per cent, with 3- and 5-year survival of 21 and 17 per cent--a decreased long-term survival compared with the neoadjuvant therapy group despite the observation that patients who underwent neoadjuvant therapy had a larger tumor size on presentation (5.5 +/- 0.4 cm vs 3.8 +/- 0.2 cm; P = 0.002). Squamous cell carcinomas seemed to be more responsive to neoadjuvant radiation and chemotherapy followed by surgery than were adenocarcinomas, with a CPR of 44.4 versus 35.5 per cent; however, 5-year survival rates in these complete responders were not significantly different (100% and 78%, respectively; P = 0.97). We report that esophagogastrectomy in conjunction with neoadjuvant therapy results in increased survival compared with surgery without neoadjuvant therapy (P < 0.01), although there may be an increased perioperative mortality associated with neoadjuvant therapy. Further studies are needed to evaluate the role of preoperative chemoradiation and to better identify the pretreatment characteristics of patients with a complete pathological response.     

P53 gene protein overexpression predicts results of trimodality therapy in esophageal cancer patients

Background. P53 protein overexpression in esophageal cancer and its correlation with response and survival after chemoradiation was retrospectively investigated.

Methods. Pretreatment and resection specimens were stained by automatic p53 immunohistochemical staining technique.

Results. P53 was expressed in 84.0% of esophagoscopy (EGD) biopsies; 71.4% of patients with metastasis of thoracoscopy/laparoscopy lymph nodes (TS/LS LN) identified by hematoxylin/eosin (H/E) were p53 (+); 14.2% of patients with negative TS/LS LN by H/E were p53 (+). Eleven out of 18 patients with p53 (+) in pretreatment EGD remained p53 (+) after chemoradiation; 38.8% of these patients had a pathological complete response (pCR). The median survival of this group was 15 months. Of 4 patients with p53 (−) pretreatment EGD, all of those were still p53 (−) after chemoradiation; 75% of these patients had pCR. The median survival was 30 months. In patients with p53 (+) TS/LS LN, 23% had a pCR after chemoradiation with a median survival of 16 months. In patients with p53 (−) TS/LS LN, 50.0% had a pCR with a median survival of 31.5 months.

Conclusions. P53 protein overexpression in pretreatment EGD and TS/LS LN may predict response to chemoradiation and survival in esophageal cancer patients.     

Clinical aspects of multimodality therapy for resectable locoregional esophageal cancer.

Radical resection has been considered the only possible way to save the lives of patients with esophageal cancer. Therefore, tremendous efforts have been made in order to improve the surgical results for resectable locoregional esophageal cancer. Various surgical approaches have been developed. Combination therapies such as neoadjuvant, adjuvant chemotherapy, and neoadjuvant chemoradiation have been extensively investigated in numerous randomized clinical trials. Due to insufficient surgical results and high postoperative mortality rates, definitive chemoradiation has been studied as alternative treatment in selected patients, based on the concept that combined-modality therapy allows simultaneous treatment of locoregional disease and systemic micrometastases. Chemoradiation has shown survival rates equivalent to surgery in some non-randomized comparative studies. Presently, concerns appear to be shifting to the question of whether definitive chemoradiation could be an alternative to surgery in the primary treatment of resectable locoregional esophageal cancer. Recently, 2 randomized trials, comparing definitive chemoradiation with chemoradiation and surgery were published. These trials seem to show at first glance that definitive chemoradiation can achieve results comparable to surgery with neoadjuvant chemoradiation. More sophisticated trials should be conducted as treatment modalities used in these trials are far from routine.     

Biomarkers for predicting the response of esophageal squamous cell carcinoma to neoadjuvant chemoradiation therapy

This review summarizes and evaluates the literature regarding the biomarkers for predicting the response and/or prognosis of esophageal squamous cell carcinoma (ESCC) patients treated with neoadjuvant chemoradiation therapy (CRT). There are seven categories of molecules known to correlate with the response and/or prognosis: tumor suppressors (p53, p21), cell cycle regulators (Cyclin D1, CDC25B, 14-3-3sigma), DNA repair molecules (p53R2, ERCC1), drug resistance proteins [metallothionein (MT)], angiogenic factors (VEGF), molecules involved in cell proliferation/invasion/metastasis (Ki-67, COX-2) and hedgehog signaling molecules (Gli-1). Of the above molecules, the tumor suppressor p53 is expected to be a representative biomarker for predicting the response and prognosis. The cell cycle markers CDC25B and 14-3-3sigma have potential as response biomarkers independent of the p53 status. The DNA repair markers, p53R2 or ERCC1, angiogenic molecule (VEGF), and hedgehog signaling pathway factor Gli-1 also have potential to predict the response and prognosis of ESCC. However, there are still many unanswered questions with regard to predicting the clinical effects of neoadjuvant CRT.     

A meta-analysis of randomized controlled trials that compared neoadjuvant chemoradiation and surgery to surgery alone for resectable esophageal cancer

BACKGROUND: Esophagectomy is a standard treatment for resectable esophageal cancer but relatively few patients are cured. Combining neoadjuvant chemoradiation with surgery may improve survival but treatment morbidity is a concern. We performed a meta-analysis of randomized controlled trials (RCTs) that compared the use of neoadjuvant chemoradiation and surgery with the use of surgery alone for esophageal cancer. METHODS: Medline and manual searches were done to identify all published RCTs that compared neoadjuvant chemoradiation and surgery with surgery alone for esophageal cancer. A random-effects model was used and the odds ratio (OR) was the principal measure of effect. Systematic quantitative review was done for outcomes unique to the neoadjuvant chemoradiation treatment group, such as pathological complete response. RESULTS: Nine RCTs that included 1,116 patients were selected with quality scores ranging from 1 to 3 (5-point Jadad scale). Odds ratio (95% confidence interval [CI]; P value), expressed as chemoradiation and surgery versus surgery alone (treatment versus control; values <1 favor chemoradiation-surgery arm), was 0.79 (0.59, 1.06; P = 0.12) for 1-year survival, 0.77 (0.56, 1.05; P = 0.10) for 2-year survival, 0.66 (0.47, 0.92; P = 0.016) for 3-year survival, 2.50 (1.05, 5.96; P = 0.038) for rate of resection, 0.53 (0.33, 0.84; P = 0.007) for rate of complete resection, 1.72 (0.96, 3.07; P = 0.07) for operative mortality, 1.63 (0.99, 2.68; P = 0.053) for all treatment mortality, 0.38 (0.23, 0.63; P = 0.0002) for local-regional cancer recurrence, 0.88 (0.55, 1.41; P = 0.60) for distant cancer recurrence, and 0.47 (0.16, 1.45; P = 0.19) for all cancer recurrence. A complete pathological response to chemoradiation occurred in 21% of patients. The 3-year survival benefit was most pronounced when chemotherapy and radiotherapy were given concurrently (OR 0.45, 95% CI 0.26 to 0.79, P = 0.005) instead of sequentially (OR 0.82, 95% CI 0.54 to 1.25, P = 0.36). CONCLUSIONS: Compared with surgery alone, neoadjuvant chemoradiation and surgery improved 3-year survival and reduced local-regional cancer recurrence. It was associated with a lower rate of esophageal resection, but a higher rate of complete (R0) resection. There was a nonsignificant trend toward increased treatment mortality with neoadjuvant chemoradiation. Concurrent administration of neoadjuvant chemotherapy and radiotherapy was superior to sequential chemoradiation treatment scheduling.     

Racial differences in prostate cancer growth: apoptosis and cell proliferation in Caucasian and African-American patients

BACKGROUND: Epidemiologic evidence reveals striking racial differences in incidence and clinical behavior of prostate cancer among American men. In this study, we assessed the incidence of apoptosis and cell proliferation in prostate cancer specimens from African-American and Caucasian patients in an attempt to identify potential differences in tumor growth determinants between the two ethnic groups. METHODS: Apoptosis and cell proliferation were analyzed in archival paraffin-embedded prostatic tumors from 44 African-American and 35 Caucasian age-matched men who underwent radical prostatectomy for localized prostate cancer. Both groups had comparable preoperative prostate-specific antigen (PSA) levels, clinical stage, and Gleason scores, and neither group of patients received neoadjuvant therapy prior to surgery. Apoptotic status in prostate tumors was evaluated in situ, using the transferase deoxyuridine end labeling (TUNEL) assay, and the expression profile of two apoptotic proteins, bcl-2 and bax. The proliferative index was determined on the basis of Ki-67 antigen immunoreactivity. RESULTS: Apoptosis in malignant prostate cells was significantly higher in African American than Caucasian men (11.6% vs. 4.2%, P < 0. 001). Interestingly, the rate of cell proliferation of prostate tumor cells was similar in the two ethnic groups (4.5% and 4.2%). The antiapoptotic protein bcl-2 was detected at significantly higher levels in tumors from Caucasian than African-American patients (40. 8% vs. 31.6%, P < 0.05). Expression of bax, the apoptosis promoter, was consistently high among tumor epithelial cells in specimens from both racial groups (68%). CONCLUSIONS: These findings provide a novel insight into the molecular determinants of tumor growth that may underlie the ethnic differences in prostate cancer incidence and clinical behavior. Downregulation of bcl-2 expression may be potentially responsible for the loss of apoptotic control in prostate tumors from African-American men. This study may have significant clinical implications in the development of novel diagnostic approaches for biologically aggressive prostate cancer from diverse racial origin.     

Multidisciplinary approach to esophageal and gastric cancer

Despite marked advances in surgical therapy for patients with esophageal, esophagogastric, and gastric cancers, the overall prognosis of these patients has not markedly improved during the past decades. Multidisciplinary approaches using adjuvant postoperative and neoadjuvant preoperative therapeutic principles have received increasing attention with regard to the management of these patients. A series of randomized, prospective trials has demonstrated that adjuvant postoperative radiation or chemotherapy does not result in a convincing survival advantage after complete tumor resection in esophageal, esophagogastric junction, or gastric cancer. The available data on the role of neoadjuvant preoperative therapy are not yet conclusive. Although neoadjuvant therapy may reduce the tumor mass in many patients, several randomized, controlled trials have shown that, compared with primary resection, a multimodal approach does not result in a survival benefit in patients with locoregional, that is, potentially resectable, tumors. In contrast, in patients with locally advanced tumors, that is, patients in whom complete tumor removal with primary surgery seems unlikely, neoadjuvant therapy increases the likelihood of complete tumor resection on subsequent surgery, but only patients with objective histopathologic response to preoperative therapy seem to benefit from this approach. Consequently, in the future, improvements in the overall survival of patients with esophageal, esophagogastric junction, or gastric cancer most likely will be achieved only by tailored therapeutic strategies that are based on the individual tumor location, tumor stage, and consideration of established prognostic factors. A clear classification of the underlying tumor entity, a profound knowledge of the prognostic factors applicable, a thorough preoperative staging, and identification of parameters that allow for the prediction of response to preoperative therapy will become essential for the selection of the optimal therapeutic modality for individual patients.     

Presence of serum p53 antibodies is associated with decreased in vitro chemosensitivity in patients with esophageal cancer

Resistance to chemotherapy remains a serious problem inhibiting the successful treatment of advanced esophageal cancer. A number of studies have revealed that p53 genetic alteration and protein overexpression can predict chemosensitivity. Furthermore, p53 protein overexpression in cancer tissues has been found to induce serum p53 antibodies (p53-Abs). This study was conducted to examine whether analysis of serum p53 Abs could predict the chemosensitivity of esophageal cancer. Serum analysis of p53 antibodies was performed by enzyme-linked immunosorbent assay in 19 patients with esophageal squamous cell carcinoma preoperatively, then surgically resected specimens were stained immunohistochemically for p53 protein expression. Tumor tissues were also analyzed for chemosensitivity by the histoculture drug response assay (HDRA) using cis-dichlorodiammineplatinum(II) (CDDP), 5-fluorouracil (5-FU), and adriamycin (ADM). Serum p53-Abs were present in 47% (9/19) of the patients and immunohistochemical analysis revealed overexpression of p53 protein in 42% (8/19) of the tumors. The presence of serum p53 antibodies was significantly correlated with p53 immunoreactivity (P = 0.005). The inhibition index of patients positive for p53-Abs was significantly lower than that of patients negative for p53-Abs (P < 0.001). This tendency was also observed in the inhibition index to 5-FU. The presence of serum p53-Abs was associated with decreased in vitro chemosensitivity to CDDP and 5-FU. Thus, the detection of serum p53-Abs is suggested to be useful for predicting chemosensitivity in patients with esophageal cancer. Received: August 2, 2000 / Accepted: March 6, 2001     

Accuracy of pathologic examination in detection of complete response after chemoradiation for esophageal cancer

BACKGROUND: Although a substantial proportion of patients undergoing neoadjuvant chemoradiation for invasive esophageal cancer develop a pathologic complete response (pCR), these patients nonetheless have a poor 5-year survival rate. We hypothesized that routine pathologic examination fails to identify some residual cancer. METHODS: Patients undergoing esophagectomy for cancer at 2 tertiary care centers were identified. Archived tumor blocks were retrieved for patients with pCR, sectioned at 50-mum intervals and reexamined for residual cancer. RESULTS: Seventy patients underwent neoadjuvant chemoradiation. Tumor blocks were available for 23 of 26 complete responders. A total of 159 blocks were reexamined. One patient was found to have a possible focus of residual invasive adenocarcinoma versus high-grade dysplasia. The remaining 22 patients had no residual disease. CONCLUSIONS: A more aggressive examination protocol for postchemoradiation esophagectomy specimens may not result in significant upstaging. Inadequate pathologic examination is likely not a major factor in the suboptimal survival in patients with pCR.     

Biomarkers for breast cancer

Molecular biomarkers for breast cancer are of several types. Risk biomarkers are those associated with increased cancer risk and include mammographic abnormalities, proliferative breast disease with or without atypia, family clustering and inherited germ-line abnormalities. Surrogate endpoint biomarkers are tissue, cellular or molecular alterations that occur between cancer initiation and progression. These biomarkers are utilized as endpoints in short-term chemoprevention trials. Prognostic biomarkers provide information regarding outcome irrespective of therapy, while predictive biomarkers provide information regarding response to therapy. Candidate prognostic biomarkers for breast cancer include elevated proliferation indices such as Ki-67 and proliferating cell nuclear antigen (PCNA); ER and PR overexpression; markers of oncogene overexpression such as c-erbB-2, TGF-a and EGFr; indicators of apoptotic imbalance including overexpression of bcl-2 and an increased bax/bcl-2 ratio; markers of disordered cell signaling such as p53 nuclear protein accumulation; alteration of differentiation signals such as overexpression of c-myc and related proteins; loss of differentiation markers such as TGF-b II receptor and retinoic acid receptor; and alteration of angiogenesis proteins such as VEGF overexpression. As our knowledge regarding molecular biomarkers for breast cancer increases, prognostic indices will be developed that combine the predictive power of individual molecular biomarkers with specific clinical and pathologic factors.     

Apoptosis in Ductal Carcinoma in Situ of the Breast

Abstract: Programmed cell death (apoptosis) may play a role in tumor development and progression. The importance of apoptosis dysregulations in ductal carcinoma in situ (DCIS) and its relationships with p53 mutations and expression of bcl-2 has received little attention in the literature. In a series of 58 DCIS patients, we evaluated the number of apoptotic cells by the TUNEL technique in subgroups of DCIS and correlated it with immunohistochemical expression of hormone receptors, c- erb B-2, p53, bcl-2, and Ki-67 (MIB-1) and DNA content measured by image cytometry. High apoptotic index (greater than 3%) was related to high tumor grade, negative hormone receptors, c- erb B-2 overexpression, aneuploidy and lack of bcl-2 immunohistochemical stain. Apoptosis was not related to p53 or proliferative index. The findings are similar to those found in infiltrating breast cancer.     

食管癌新辅助放化疗疗效预测分子标志物

局部晚期食管癌单纯手术治疗预后较差,新辅助放化疗并手术治疗的方案可明显延长食管癌患者的总体生存时间.目前,该治疗方案已成为欧美国家及我国对局部晚期食管癌进行规范化治疗的指南.然而,由于只有经新辅助放化疗后获得病理缓解的患者可从中获益,治疗无反应的患者预后可能比单纯手术更差.因此,预测食管癌新辅助放化疗的疗效,区分优势人群和耐受人群,从而实现个体化的治疗极为重要.分子标记物用于预测食管癌新辅助放化疗的疗效研究前景广阔,有望广泛应用于临床实践,指导局部晚期食管癌个体化治疗方案的决策.     

Is MIB-1 proliferation index a predictor for response to neoadjuvant therapy in patients with esophageal cancer?

BACKGROUND: The overall survival rate for patients with an esophageal cancer remains poor. As a consequence, preoperative chemoradiation was introduced for patients with tumor stage T >1 M0 regardless of tumor histology or localization. However, factors predicting response to this therapy pretherapeutically are largely unknown. METHODS: Clinical results of preoperative chemoradiation were investigated. The rates of proliferation and apoptosis were determined in pretherapeutic tumor samples and correlated with tumor response and long-term survival after surgery. RESULTS: A complete tumor response due to chemoradiation (n = 42; cervically localized tumors excluded) was achieved in 11 patients (26%) after resection. Five-year survival rate was significantly improved in these patients compared with those who did not respond to chemoradiation (48% versus 5.5%; P = 0.003). Chemoradiation was performed without benefit in 43%. Perioperative hospital mortality rate was 14.3% in all patients. No correlation of apoptosis with response to chemoradiation or postoperative long-term survival was observed. However, there was a clear correlation between the proliferation rate as determined by MIB-1 immunohistology. Five-year survival rate of patients with a proliferation index (PI) >/=39% was 38% compared with 0% in tumors with a PI <39%. Tumors with a PI >/=39% responded to chemoradiation in 71.4%, but 100% of tumors with a PI <39% did not. Mean survival time of these patients was 33 months and 11 months, respectively (P = 0.015). CONCLUSIONS: The results indicate that the PI may be used for stratification of patients treatment prior surgery. However, these results need further validation in larger patient numbers in the search for factors indicating response pretherapeutically to preoperative chemoradiation in esophageal cancer.     

Salvage radical prostatectomy for radio-recurrent prostate cancer: is this a viable option?

The role of salvage prostatectomy for radio-recurrent prostate cancer remains unclear. Recurrent prostate cancer after radiation therapy is in many cases biologically aggressive. It is unclear whether the biologic aggressiveness of radio-recurrent prostate cancer is due to time-dependent cancer clonal evolution (potentially induced by radiation damage), or is due to an innately aggressive tumor secondary to overexpression or mutation of apoptotic inhibitors that render these tumors resistant to radiation. Recent studies examined the role of DNA ploidy, p53 and bcl-2 expression, proliferative indices and glutathione S-transferase-pi in predicting response to radiation therapy or salvage prostatectomy. Because of the potential for significant morbidity after salvage prostatectomy, preoperative parameters that aid in the identification of the patients who are most likely to benefit from surgery are needed.     

Preclinical study of adenoviral p53 gene therapy for esophageal cancer

An alteration of the p53 gene function is a major factor in the development of esophageal cancer. Recently, p53 gene therapy has been applied for clinical studies in lung cancer and head and neck cancer. However, no preclinical studies have yet demonstrated an anticancer effect of adenoviral-mediated wild-type p53 gene therapy on esophageal cancer. We herein evaluated the effect of p53 adenoviral gene therapy on human esophageal squamous cell carcinoma to test the ability of clinical application. A normal esophageal epithelial cell line (EN53F) and two human esophageal cancer cell lines (ECGI-10 and T.Tn) with a p53 alteration were used. The transduction efficiency, p53 protein expression, p21 protein expression, the induction of apoptosis, and growth suppression were assessed by using the recombinant adenoviral vector Ad5CMV-p53. The transduction efficiency was 60%–80% at 100 plaque-forming units (PFU)/cell and 80%–100% at 300 PFU/cell. A significant growth suppression following an Ad5CMV-p53 infection was observed in both cancer cell lines. A Western blot analysis confirmed the presence of both exogenous p53 protein expression and p21 protein induction. Apoptotic cell death was observed with TUNEL staining. T.Tn xenografts in nude mice transduced with Ad5CMV-p53 demonstrated significant growth suppression. These data suggest that Ad5CMV-p53 may thus be a potentially effective therapeutic agent for locally advanced esophageal cancer. Received: July 19, 2000 / Accepted: January 9, 2001