Identification of a novel SEREX antigen family, ECSA, in esophageal squamous cell carcinoma.

BACKGROUND: Diagnosis of esophageal squamous cell carcinoma (SCC) may improve with early diagnosis. Currently it is difficult to diagnose SCC in the early stage because there is a limited number of tumor markers available. RESULTS: Fifty-two esophageal SCC SEREX antigens were identified by SEREX (serological identification of antigens by recombinant cDNA expression cloning) using a cDNA phage library and sera of patients with esophageal SCC. Sequence analysis revealed that three of these antigens were similar in amino acid sequences, and they were designated as ECSA (esophageal carcinoma SEREX antigen)-1, -2 and -3. The ECSA family was also similar to an EST clone, hepatocellular carcinoma-associated antigen 25a (HCA25a). Serum antibody levels to ECSA-1, -2 and -3 were significantly higher in patients with esophageal SCC than in healthy donors. Based on the conserved amino acid sequences, three peptides were synthesized and used for enzyme-linked immunosorbent assays (ELISA). The serum antibody levels against one of these peptides were significantly higher in patients with esophageal SCC. This peptide sequence was also conserved in FAM119A, GOSR1 and BBS5, suggesting that these are also ECSA family members. Reverse transcription followed by quantitative PCR analysis showed that the mRNA expression levels of ECSA-1, -2 and -3 and FAM119A but not of HCA25a, GOSR1 and BBS5 were frequently elevated in esophageal SCC tissues. CONCLUSIONS: We have identified a new gene family designated ECSA. Serum antibodies against the conserved domain of the ECSA family may be a promising tumor marker for esophageal SCC.

Viral shedding after p53 adenoviral gene therapy in 10 cases of esophageal cancer.

We detected adenoviral DNA fragments in excretions of 10 esophageal cancer patients by DNA-PCR after tumor injection of Ad-CMV-vector. A total of 220 samples consisting of feces, gargling saliva, urine, and blood plasma were assessed. A total of 29.7% of feces samples and 13.2% of gargling saliva samples were positive for adenoviral DNA fragments, but 89.7% of the positive feces samples and all of the positive gargling saliva samples turned negative on day 12 after tumor injection. Although adenoviral DNA fragments may be pathogen-free, patients' feces and gargling saliva contain adenoviral DNA fragments for 12 days after injection.

Decrease in chemosensitivity against anticancer drugs by an esophageal squamous cell carcinoma SEREX antigen, AISEC.

We performed SEREX (serological identification of antigens by recombinant cDNA expression cloning) using the sera of patients with esophageal squamous cell carcinoma (SCC), and examined whether some of the SEREX antigens can affect chemosensitivity against anticancer drugs. We isolated a novel gene which was designated as AISEC (antigen identified by SEREX for esophageal carcinoma). RT-PCR analysis showed that the mRNA expression levels of AISEC were higher in esophageal SCC tissues than in their normal counterparts. By transfection into activated Ha-ras-transformed NIH3T3 (ras-NIH) mouse fibroblasts, we isolated a clone, FAISEC-3, which stably expressed AISEC. FAISEC-3 cells were more resistant to anticancer drugs, such as mitomycin C, ifosfamide, vincristine, camptothecin and etoposide, than parental ras-NIH cells. Luciferase reporter assay after a transient transfection with AISEC cDNA or the control vector revealed that the transactivity of p53 was suppressed by AISEC in a dose-dependent manner. These results suggested that esophageal SCC tissues produce AISEC in increased amounts, which can reduce the chemosensitivity against anticancer drugs possibly by suppressing the p53 transactivation ability.

Identification of Makorin 1 as a novel SEREX antigen of esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (SCC) represents one of the most malignant tumors. To improve the poor prognosis, it is necessary to diagnose esophageal SCC at early stages using new tumor markers. SEREX (serological identification of antigens by recombinant cDNA expression cloning) is suitable for large-scale screening of tumor antigens and has been applied for various types of human tumors. METHODS: Tumor markers of esophageal squamous cell carcinoma (SCC) were screened by SEREX method. The presence of serum anti-makorin 1 (MKRN1) antibodies (s-MKRN1-Abs) was examined by Western blotting using bacterially expressed MKRN1 protein. The expression levels of MKRN1 mRNA in tissues were examined by RT-PCR. The biological activity of MKRN1 was examined by transfection of ras-NIH3T3 mouse fibroblasts with MKRN1 cDNA. Major ubiquitinated proteins in MKRN1-transfected cells were identified by immunoprecipitation with anti-ubiquitin antibody followed by mass spectrometry. RESULTS: MKRN1 was identified as a novel SEREX antigen of esophageal SCC. Although a total of 18 (25%) of 73 patients with esophageal SCC had s-MKRN1-Abs, none of the 43 healthy donors had a detectable level of s-MKRN1-Abs. There was no correlation between the presence of s-MKRN1-Abs and clinicopathological variables other than histological grading. Well-differentiated tumors were associated significantly with the presence of s-MKRN1-Abs in the patients. The mRNA levels of MKRN1 were frequently higher in esophageal SCC tissues than in the peripheral normal esophageal mucosa. Stable transfection of ras-NIH3T3 cells with MKRN1 cDNA induced prominent morphological changes such as enlargement of the cell body and spreading. Ubiquitination of 80- and 82-kDa proteins were clearly observed in MKRN1-transfected cells but not in the parental cells, which were identified as L-FILIP (filamin A interacting protein 1). CONCLUSION: MKRN1 is a novel SEREX antigen of esophageal SCC, and s-NKRN1-Abs can be a candidate of diagnostic markers of esophageal SCC with high specificity. It is plausible that MKRN1 is involved in carcinogenesis of the well-differentiated type of tumors possibly via ubiquitination of L-FILIP.

Detection of anti-CUEC-23 antibodies in serum of patients with esophageal squamous cell carcinoma: a possible new serum marker for esophageal cancer.

BACKGROUND: Serological identification of antigens by recombinant cDNA expression cloning (SEREX) is an established method for detecting new tumor-specific antigens. Antibodies to SEREX antigens may be useful for the detection of esophageal squamous cell carcinoma (SCC). METHODS: A phage cDNA library of a human esophageal SCC cell line was screened using sera of patients with esophageal SCC. The presence and levels of serum antibodies to SEREX antigens were established by Western blotting and enzyme-linked immunosorbent assay (ELISA) using purified recombinant antigen proteins, respectively. RESULTS: The newly identified esophageal SCC antigen is encoded by a novel gene located on chromosome 1, here designated CUEC-23. Serum CUEC-23-antibodies (s-CUEC-23-Abs) were detected in 14 of 54 patients with esophageal SCC (26%) by Western blot analysis. Esophageal SCCs were positive for s-CUEC-23-Abs together with CEA, SCC-Ag or CYFRA21-1 in 44, 41 and 52% of cases, respectively. There was no detectable association between the presence of s-CUEC-23-Abs and clinicopathological variables. ELISA showed that the levels of s-CUEC-23-Abs were significantly higher in patients with esophageal SCC than in healthy volunteers (17% in the former using the mean+3 SD of s-CUEC-23-Abs in healthy controls as the cutoff). CONCLUSION: A new tumor antigen, CUEC-23, was identified by SEREX screening. s-CUEC-23-Abs might be a useful serum marker to detect esophageal SCC.

Impact of lymph node involvement in T2 or T3 thoracic esophageal squamous cell carcinoma.

BACKGROUND/AIMS: Treatment strategy for T2/ T3 esophageal carcinoma has become controversial because of recent improvements in chemoradiation therapy. Only a few study analyzed the prognostic impact of clinicopathological factors for surgical outcome of patients with esophageal carcinoma focused on T2/T3 tumors. METHODOLOGY: Subjects of this study were 187 patients with pathological T2 (n = 46) or pathological T3 (n = 141) thoracic esophageal squamous cell carcinoma who received surgical treatment without neoadjuvant therapy. The impact of clinicopathological factors on survival was evaluated by univariate and multivariate analysis. RESULTS: Overall 5-year survival rate of all patients was 38%. Dismal 5-year overall survival rates were observed in patients with 5 or more positive nodes (11%). Multivariate analysis indicated that lymph node metastases (hazard ratio; 2.07, 95%IC, 1.20-3.56, p < 0.01) and the number of metastatic nodes (hazard ratio; 1.77, 95%IC, 1.11-2.82, p = 0.02) were independent risk factors for poor survival. However, tumor depth itself was not an independent risk factor for survival. CONCLUSIONS: Although survival of patients with pathological T2 or T3 was partly dependent on tumor depth, it was mainly dependent on lymph node status. Multiple positive nodes were independent risk factors for poor survival.

Serum anti-myomegalin antibodies in patients with esophageal squamous cell carcinoma.

In order to identify new serum markers of esophageal squamous cell carcinoma (SCC), we performed serological identification of antigens by recombinant cDNA expression cloning (SEREX). E. coli was transformed with a lambdaZAPII phage cDNA library prepared from mRNA of an esophageal cancer cell line (T.Tn), and IPTG-induced cDNA products were screened for interaction with antibodies in allogeneic sera of patients with esophageal SCC. We identified myomegalin (MMGL, phosphodiesterase 4D interacting protein/PDE4DIP) as a new SEREX antigen for esophageal SCC. Western blot analysis revealed that serum anti-myomegalin antibodies (s-MMGL-Abs) were present in 43 (47%) of 91 patients, but in only one (2.2%) of 45 healthy controls. Of the 21 patients with stage I disease, 8 (38%) were sero-positive. The positive rate of s-MMGL-Abs was greater than those of other conventional tumor markers. Reverse transcription-PCR analysis suggested that alternative splicing from myomegalin variant 1 to variant 5 may explain, in part, the development of s-MMGL-Abs. Although the presence of s-MMGL-Abs was not related to any clinicopathological features of the patients, multivariate analysis indicated that the presence of s-MMGL-Abs was significantly associated with a favorable prognosis. Consequently, s-MMGL-Abs may be a useful tumor marker to diagnose and establish a prognosis in patients with esophageal SCC.

Sensitization against anticancer drugs by transfection with UBE2I variant gene into ras-NIH3H3 mouse fibroblasts.

We previously performed SEREX (serological identification of antigens by recombinant expression cloning) using the sera of patients with esophageal squamous cell carcinoma (SCC), and isolated a variant clone (AK093616) of ubiquitin-conjugating enzyme E21 (UBE2I). This clone was tentatively designated as UBE2I-v5 and analyzed for biological function by transient transfection of the cDNA into activated Ha-ras-transformed NIH3T3 (ras-NIH) mouse fibroblasts. Chemosensitivity to 92 cytotoxic drugs was compared between UBE2I-v5-transfected cells and the parental ras-NIH cells. The UBE2I-v5-transfected cells were more sensitive than the parental cells to anticancer drugs such as vincristine (VCR), mitoxantrone (MIT) and etoposide (VP16). The regression analysis of the total chemosensitivity pattern of UBE2I-vS-transfected cells revealed that the function of UBE2I-v5 was positively related to RPA2 (replication protein A2), Rho-GDI (Rho guanine nucleotide dissociation inhibitor a), FUS (putative tumor suppressor) and TKT (transketolase) but negatively related to Per-1 (period-I), Ran (nuclear Ras-related protein), PTEN (phosphatase and tensin homolog), C/EBPalpha (CCAAT/enhancer binding protein a) and the tumor suppressor p53. Thus, it is possible that UBE21-v5 plays a role in carcinogenesis by suppressing the function of CIEBPa and/or p53 via RPA2-like activity.

Is the surgical stress associated with worse survival in patients with esophageal cancer?--Analysis of colon substitution for 37 patients with remnant stomach.

BACKGROUND/AIMS: Colon substitution is a standard method of reconstruction, although an aggressive surgery, for patients with esophageal carcinoma who have remnant stomach. Presence of postoperative complication was reported to be a risk factor for worse survival in the patients with esophageal cancer. We evaluated the affect of this surgical stress on the postoperative course and long-term survival of patients with esophageal carcinoma. METHODOLOGY: Between 1980 and 2002, a total of 37 patients with primary thoracic esophageal squamous cell carcinoma, who had history of gastrectomy due to gastric ulcer, underwent R0 esophagectomy followed by colon substitution (colon group). The clinical affect of colon substitution was retrospectively evaluated in comparison with gastric substitution as the control group (stomach group). RESULTS: The postoperative hospital morbidity rate was significantly higher in the patients with remnant stomach than in the control group. Although the clinicopathological features in both groups were similar, except operative time and bleeding volume, the overall and cause-specific survival of the remnant stomach group were significantly worse than those of the control group. Multivariate analysis suggested that remnant stomach was an independent risk factor for a worse survival. CONCLUSIONS: Surgical stress and postoperative complications, resulted by colon substitution for the patients with remnant stomach, might be associated with worse survival of patients with esophageal cancer.

Surgical outcome of patients with thoracic esophageal cancer positive for cervical lymph nodes.

BACKGROUND/AIMS: Although cervical lymph nodes were classified as distant metastases in patients with thoracic esophageal cancer, not a few patients survive more than five-years. The purpose of this study was to predict patients with good prognosis among thoracic esophageal cancer patients with cervical node metastases. METHODOLOGY: From 1983 to 2002, 312 consecutive patients with thoracic esophageal squamous cell carcinoma underwent curative surgery with 3-field lymph node dissection (3FLD). A total of 88 (28%) of 312 patients were diagnosed with cervical lymph node metastases. Univariate and multivariate analyses were carried out to evaluate the impact of clinico-pathological factors on the survival of these patients. RESULTS: Overall five-year survival rate of 88 patients with cervical lymph node metastases was 26%. Univariate analysis revealed that following groups showed more than 40% overall five-years survival rate; female patients, patients with T1, T2 tumors and patients without thoracic node metastases. These variables were also independent good prognostic factors in multivariate analysis. CONCLUSIONS: Although cervical lymph node metastases was risk factors for worse survival, female patients, patients with T1, T2 tumors and patients without thoracic node metastases showed acceptable overall survival after 3FLD.

Location and clinical impact of solitary lymph node metastasis in patients with thoracic esophageal carcinoma.

BACKGROUND: The location and clinical impact of solitary lymph node metastasis from thoracic esophageal carcinoma have not been evaluated sufficiently. METHODS: A consecutive series of 91 patients with a solitary positive lymph node who underwent curative surgery for thoracic esophageal carcinoma was investigated. The prognostic impact was evaluated by univariate analysis and multivariate analysis using Cox's proportional hazards model. RESULTS: A total of 52 (57%) of the 91 patients showed a solitary positive node beyond the thorax. While 29% of the patients with an upper thoracic tumor showed a cervical node, 13% of the patients with a middle tumor and none of the patients with a lower tumor showed a cervical node. Tumor depth and venous invasion were found to be independent risk factors for poor survival. CONCLUSIONS: The solitary positive lymph nodes were broadly distributed depending on the tumor location and tumor depth. Tumor depth and venous invasion were risk factors for poor survival in these patients.

Prediction of lymph node status in patients with superficial esophageal carcinoma: analysis of 160 surgically resected cancers.

BACKGROUND: The ability to predict lymph node metastasis in cases of superficial esophageal carcinoma before surgery would allow the identification of specific patients who do not require additional surgical resection after endoscopic local resection. METHODS: From 1980 to 2002 a total of 160 patients with superficial esophageal carcinoma, Tis or T1 tumors, underwent subtotal esophagectomy with lymph node dissection. On the basis of clinicopathologic data the risk factors for lymph node metastases are discussed. RESULTS: Patients with tumors that showed submucosal invasion, a nonflat shape, and lymphatic invasion had a higher risk for lymph node metastasis than the other patients. Multivariate analysis showed that the tumor depth and the macroscopic shape of the tumor were independent risk factors for lymph node metastases. CONCLUSIONS: Esophagectomy with lymph node dissection is recommended for patients with submucosal cancer. Local tumor resection can be recommended for patients with mucosal cancer without lymphatic invasion.

Synergistic antitumor effect of antiangiogenic factor genes on colon 26 produced by low-voltage electroporation.

Antiangiogenic factors are potent endothelial cell growth inhibitors that have been shown to inhibit angiogenesis in vitro and tumor growth in mice. We have demonstrated the synergistic antitumor effect of antiangiogenic genes (mouse angiostatin: pBLAST-mAngio; and mouse endostatin: p-BLAST42-mEndo XV) delivered to tumors by low-voltage electroporation in mouse colon 26 models. A synergistic antitumor effect was strongly suggested by in vivo tumor growth kinetics, as well as in survival studies with the mice. RT-PCR confirmed that the fragments of each gene were transferred by low-voltage electroporation in the tumor. Decreased microvessel density measurements in tumors also confirmed the efficacy of the synergistic antitumor effect of both genes. Significant growth inhibition was observed in mice treated with a 1:1 proportion of angiostatin and endostatin genes, and the order of the both genes transferred (first the endostatin gene, followed 1 week later by the angiostatin gene) had a profound inhibitory effect on tumor growth. These data suggest that in vivo delivery of antiangiogenic genes with low-voltage electroporation could be a possible therapeutic strategy for established solid tumors when both genes were applied in combination.

Prognostic significance of serum p53 antibody in patients with esophageal squamous cell carcinoma.

BACKGROUND: The p53 protein overexpression that usually results from genetic alterations has been reported to induce serum antibodies against p53. There is little information about the clinicopathologic and prognostic significance of preoperative serum p53 antibody in patients with esophageal cancer. METHODS: A highly specific enzyme-linked immunosorbent assay was used to analyze serum p53 antibodies in 105 patients with esophageal squamous cell carcinoma. The cutoff level of 1.3 U/mL was used to indicate seropositive patients, and the cutoff level of 10 U/mL was used to identify high titer patients. At 3 months after surgery, seropositive patients were examined again. RESULTS: A total of 28 patients (26.7%) were positive for serum p53 antibodies. The patients who remained seropositive were more likely to develop tumor recurrence (P =.025). Seropositive patients had worse outcome than seronegative patients. The high titer group had significant association with advanced tumor stages and worse outcomes than the low titer group. High serum p53 antibody titer was an independent prognostic factor (P <.001). CONCLUSIONS: We found that serum p53 antibody was useful to detect esophageal cancer and to identify those with a high risk of tumor recurrence and a poor prognosis.

Prediction of survival with squamous cell carcinoma antigen in patients with resectable esophageal squamous cell carcinoma.

BACKGROUND: Increased preoperative serum squamous cell carcinoma antigen (SCC-Ag) concentrations have been found to be associated with advanced stage and poor prognosis in lung and cervical cancers. Because little was known about the significance of SCC-Ag concentration in patients with esophageal cancer, the aim of this study was to analyze the clinicopathologic significance of SCC-Ag in patients with esophageal SCC. PATIENTS AND METHODS. Preoperative SCC-Ag concentration was measured with enzyme-linked immunosorbent assay in 309 patients with primary esophageal SCC. All patients underwent curative radical surgery without any preoperative therapy. In 215 of 309 patients, carcinoembryonic antigen (CEA) was also measured to compare clinical significance of CEA with that of SCC-Ag. The prognostic significance for survival of SCC-Ag concentrations was studied with multivariate analysis with Cox proportional hazards model. RESULTS: The SCC-Ag concentration and the positivity rate of SCC-Ag were significantly elevated in patients associated with tumor progression. Statistically significant differences in SCC-Ag concentrations and SCC-Ag positivity rates were observed depending on tumor size, tumor depth, lymph node status, and distant metastasis. Although CEA was not a prognostic factor (P =.21), a high SCC-Ag concentration was a significant prognostic factor (P <.01). Multivariate analyses indicated that T factor had the best predictive power, but SCC-Ag concentration contained additional, independent prognostic information. CONCLUSION: Our findings suggest that preoperative serum SCC-Ag concentrations might provide a predictive information for tumor progression and survival in patients with esophageal SCC.

Treatment response and prognosis of patients after recurrence of esophageal cancer.

BACKGROUND: Although radical operation and adjuvant chemoradiotherapy improve survival in patients with advanced esophageal cancer, more than half of these patients have recurrence. The aim of this study was to explore treatment responses and prognostic factors in patients with recurrent esophageal cancer. METHODS: The operative specimens from 258 patients undergoing radical esophagectomy with extended lymphadenectomy for esophageal squamous cell carcinoma between 1990 and 1999 were analyzed. Depth of tumor invasion, and the extent and location of lymph node metastases were determined. Postoperative recurrence was identified from positive findings on successive 3-month examinations of tumor markers, 6-month examinations of ultrasonography, and annual computed tomography. Of 258 patients, 95 had recurrence by the end of 2000 (mean follow-up was 22 months, range, 2-113). Of those 95 patients, 76 received nonsurgical treatment, 7 received operative intervention, and 12 received no treatment. Clinicopathologic features of recurrent tumors were analyzed to determine prognostic values. Serum anti-p53 antibodies (S-p53-Abs), serum C-reactive protein concentration (S-CRP), and albumin concentration were also analyzed. RESULTS: The main recurrent patterns were nodal (n = 45) and organ (n = 35). Of the nonsurgical treatment group, 47 patients received chemoradiotherapy; 17, chemotherapy; and 12, radiotherapy. Overall clinical response was observed in 26 of 76 patients (34%). Treatment response was significantly associated with the type of recurrence, history of perioperative adjuvant therapy, time of recurrence, number of recurrent tumors, albumin concentration, S-CRP, and S-p53-Abs. Multivariate analysis suggested that S-p53-Abs and S-CRP were independent prognostic factors. CONCLUSION: The status of S-p53-Abs and S-CRP may predict response and outcome of patients with recurrence of esophageal cancer after radical operation.

Prognostic significance of CYFRA 21-1 in patients with esophageal squamous cell carcinoma.

BACKGROUND: CYFRA 21-1 has been reported as a useful tumor marker for esophageal carcinoma, but little information was reported about the clinicopathologic importance of CYFRA 21-1. The aim of this study was to analyze the clinicopathologic and prognostic significance of preoperative CYFRA 21-1 in patients with esophageal squamous cell carcinoma. STUDY DESIGN: The CYFRA 21-1 levels were measured before surgery by enzyme-linked immunosorbent assays in 157 patients with primary esophageal squamous cell carcinomas using 3.5 ng/mL as the upper limit of normal. All patients underwent radical surgical procedures without any preoperative therapy. The association between the clinicopathologic factors assessed and the CYFRA 21-1 level was determined. The CYFRA 21-1 values were monitored after surgery in 45 available patients. The prognostic values were determined by multivariate analysis using Cox's proportional hazards model. RESULTS: Thirty-one of the 157 patients (19.7%) had high CYFRA 21-1 levels (> or =3.5 ng/mL). CYFRA 21-1 levels were significantly increased in patients with large tumors (> or =40 mm, p = 0.009), deep tumors (T2-T4, p = 0.003), and node-positive tumors (p = 0.003). CYFRA 21-1 levels significantly decreased after surgery (p < 0.001). A high CYFRA 21-1 level before surgery was an independent prognostic factor for survival (p = 0.043). CONCLUSIONS: A high CYFRA 21-1 level is associated with tumor progression and poor survival in patients with esophageal squamous cell carcinoma.

Lymphoepithelioma-like esophageal carcinoma with macroscopic reduction.

Esophageal lymphoepithelioma-like carcinoma (LELC) is extremely rare. We report the first case of esophageal LELC showing macroscopic reduction. A 67-year-old male presented with dysphagia and, by endoscopic examination, was found to have a significantly raised tumor of 10 mm in diameter in the thoracic esophagus. The biopsied material showed esophageal cancer. We performed endoscopic submucosal dissection. However, the tumor became flattened, similar to a scar, in only 2 mo. Histologically, the carcinoma cells had infiltrated the submucosal layer. Prominent infiltration of T lymphoid cells that stained positive for CD8 was observed around the carcinoma cells. Therefore, this lesion was considered to be an LELC with poorly differentiated squamous cells. Because the margin was positive, an esophagectomy was performed. Carcinoma cells were detected in the neck in one lymph node. The staging was T1N0M1b. However, the patient has been well, without adjuvant therapy or recurrence, for more than 5 years.

Mode of lymphadenectomy and surgical outcome of upper thoracic esophageal squamous cell carcinoma.

INTRODUCTION: Only a few studies have evaluated the impact of clinicopathological variables and cervical lymphadenectomy on survival in patients with upper thoracic esophageal squamous cell carcinoma (SCC). MATERIAL AND METHODS: From 1960 to 2005, a total of 167 consecutive patients with upper thoracic esophageal SCC underwent esophagectomy. Of these patients, 108 underwent surgery between 1960 and 1989 and 59 between 1990 and 2005. A total of 65 patients were treated with cervical lymphadenectomy. Univariate and multivariate analyses were performed to evaluate the impact of clinicopathological variables on surgical outcome and possible predictors for cervical lymph node metastasis. RESULTS AND DISCUSSION: The overall 5-year survival of the later period was significantly better than the former period (43% vs 13%, p < 0.01). Based on Cox's proportional hazards model, T3/T4 tumors, thoracic or abdominal node metastasis, venous invasion, residual cancer, absence of cervical lymphadenectomy, and hospital morbidity were independent risk factors for reduced survival in patients with upper thoracic esophageal SCC. A total of 31 (48%) of 65 patients who underwent cervical lymphadenectomy showed positive nodes in cervical field. CONCLUSION: Based on logistic regression analysis, T3/T4 tumors and recurrent nerve node metastasis were possible risk factors for cervical node metastasis.

Perioperative changes of serum p53 antibody titer is a predictor for survival in patients with esophageal squamous cell carcinoma.

BACKGROUND: Although the presence of serum p53 antibody (s-p53-Abs) before treatment has been shown to correlate with poor prognosis and lymph node metastasis in esophageal cancer, there has been little information about postoperative s-p53-Abs titer and perioperative changes of s-p53-Abs titers in patients with esophageal carcinoma. METHODS: A highly specific enzyme-linked immunosorbent assay was used to analyze s-p53-Abs in 110 patients with esophageal squamous cell carcinoma before and 1 month after surgery. The cutoff level of 1.3 U/ml was used to indicate seropositive patients. Impact of postoperative s-p53-Abs titer and perioperative changes of s-p53-Abs on survival was evaluated. RESULTS: Forty (36%) of 110 patients were positive for s-p53-Abs before surgery and 35 patients (32%) were positive after surgery. s-p53-Abs titer generally decreased after surgery. Among sero-positive patients, the patients who remained sero-positive after surgery (n = 28) had a worse prognosis than patients who showed sero-conversion (P = 0.02). Among sero-positive patients, the nondecreased titer group showed significantly unfavorable survival (P < 0.01). Multivariate analysis revealed that postoperative s-p53-Abs was an independent risk factor for worse overall survival (adjusted hazard ratio = 3.05; 95% confidence interval = 1.11-8.33; P = 0.03). CONCLUSIONS: Perioperative monitoring of s-p53-Abs titers was useful to identify patients with esophageal cancer with a high risk for tumor recurrence and a poor prognosis. Continuous sero-positive patients and/or nondecreased titer group, even after surgery, showed significantly unfavorable survival.