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A G Casson

Publications and source records attributed to A G Casson.

At least 19 recordsLinked to original sources
PubMed2000

What is the optimal distal resection margin for esophageal carcinoma?

BACKGROUND: Whereas a proximal resection margin of 12 cm is recommended for complete resection of esophageal cancer, the extent of distal resection is unclear. METHODS: We examined distal resection margins in a consecutive series of patients who underwent esophagectomy for squamous cell carcinomas (n = 50), primary esophageal adenocarcinomas (n = 100), and adenocarcinomas of the cardia (n = 39), in whom all macroscopic tumor was judged to be completely resected. RESULTS: Microscopic tumor was found at a 3-cm distal resection margin for one multifocal squamous cell carcinoma. Positive distal resection margins were seen in 12% (12 of 100 patients) of primary esophageal adenocarcinomas (median, 2 cm versus 4 cm if negative; p = 0.002, Wilcoxon) and 28% (11 of 39 patients) of cardia adenocarcinomas (median, 1 cm versus 3 cm if negative; p = 0.02, Wilcoxon). Although pathologic stage was shown to be the only significant predictor of overall survival (Hazard ratio [HR] 1.8; 95% confidence interval 1.2 to 2.6; p = 0.007), there was a trend toward reduced postoperative survival for patients with histologically positive distal resection margins, in particular for patients with cardia adenocarcinomas (median, 15.4 months versus 5.7 months if negative; p = 0.0001). CONCLUSIONS: To achieve consistently negative distal resection margins, we recommend resection of at least 5 cm of macroscopically normal foregut below the distal margin of the primary tumor.

Adenocarcinoma↗
PubMed2000

A study of smoking, p53 tumor suppressor gene alterations and non-small cell lung cancer.

PURPOSE: The purpose of this study was to investigate the relationship between smoking and p53 tumor suppressor gene alterations, and their association with clinicopathologic features and prognosis in non-small cell lung cancer (NSCLC). METHODS: For 111 of 119 stage I-III NSCLC patients that had been followed prospectively, tumor p53 protein accumulation was measured immunohistochemically (IHC). Staining was evaluated as a score (p53IHCS) combining intensity and percent distribution. RESULTS: Forty-eight of 111 (43%) tumors had p53IHCS > 1. p53 IHC was associated with increasing tumor size (T) (p = 0.035), nodal status (N) (p = 0.091), stage (p = 0.054), and histology: squamous cell carcinoma (70%) and adenocarcinoma (27%) (p = 0.0002). In logistic regression analysis, p53 IHC was associated with squamous cell histology versus other histotypes [adjusted odds ratio (OR)5.90, 95% confidence interval (CI) 2.34-14.90]. p53 IHC was not associated with smoking variables. In multivariate proportional hazards analysis, p53IHCS and pack-years smoked (PY), both as continuous variables, were negative prognostic factors. The adjusted hazard ratios (HR) for the survival outcome recurrence for p53IHCS and PY were 1.20 (95% CI 1.02-1.40) and 1.03 (95% CI 1.01-1.04), and for death due to recurrent disease (DRD) were 1.35 (95% CI 1.11-1.64) and 1.03 (95% CI 1.01-1.04), respectively. Comparing the 75th percentile to the baseline 0, the adjusted HR for p53IHCS (5 vs. 0) was 4.5 and for PY (55 vs. 0) was 5.1 for the outcome DRD. Both variables demonstrated a dose-response relationship with survival. CONCLUSIONS: PY and p53IHCS are significant, independent and important predictors of recurrence and DRD in stage I-III NSCLC.

Adenocarcinoma↗
PubMed1999

Molecular evolution of the metaplasia-dysplasia-adenocarcinoma sequence in the esophagus.

The incidence of adenocarcinoma of the esophagus has been increasing in developing countries over the last three decades and probably reflects a genuine increase in the incidence of its recognized precursor lesion, Barrett's metaplasia. Despite advances in multimodality therapy, the prognosis for invasive esophageal adenocarcinoma is poor. An improved understanding of the molecular biology of this disease may allow improved diagnosis, therapy, and prognosis. We focus on recent developments in the molecular and cell biology of Barrett's metaplasia, a heterogeneous lesion affecting the transitional zone of the gastro-esophageal junction whose associated molecular alterations may vary both in nature and temporally. Early premalignant clones produce biological and genetic heterogeneity as seen by multiple p53 mutations, p16 mutations, aneuploidy, and abnormal methylation resulting in stepwise changes in differentiation, proliferation, and apoptosis, allowing disease progression under selective pressure. Abnormalities in expression of growth factors of the epidermal growth factor family and cell adhesion molecules, especially cadherin/catenin complexes, may occur early in invasion. Exploitation of these molecular events may lead to a more appropriate diagnosis and understanding of these lesions in the future.

Adenocarcinoma↗
PubMed1999

Surgeons' assessment of symptoms suggesting extrathoracic metastases in patients with lung cancer. Canadian Lung Oncology Group.

BACKGROUND: In patients with apparently operable non-small cell lung cancer (NSCLC), clinicians often omit investigation for M disease in asymptomatic patients. Previous investigations have not specified in detail what is meant by "symptomatic," and this could differ between surgeons. We have investigated the extent to which surgeons' criteria differ for presence of symptoms. METHODS: Participating surgeons from seven centers, enrolled patients they judged "asymptomatic" in a randomized trial of investigational strategies for NSCLC. Patients completed a structured questionnaire describing symptoms of the central nervous system (CNS). In 685 patients, we documented CNS symptom recurrence after resectional surgery over 1 year of follow-up. RESULTS: Two centers enrolled only patients without even the mildest symptoms. Three centers took an intermediate approach, occasionally classifying patients with mild symptoms as "asymptomatic" and thus enrolling them in the trial. Two centers classified an appreciable number of patients with minimal symptoms, and occasionally with more than minimal symptoms, as "asymptomatic." Patients with even mild CNS symptoms were more likely to subsequently present with CNS metastases. CONCLUSIONS: Thoracic surgeons differ in their ideas of what may constitute the symptoms of M disease. Patients with structured questionnaire results that suggest symptoms of CNS disease are more likely to have CNS symptom recurrence after resectional surgery.

Bone Neoplasms↗
PubMed1999

Characterization of cytochrome P450 expression in human oesophageal mucosa.

The expression of cytochrome (CYP) P450 enzymes in human oesophageal mucosa was investigated in a total of 25 histologically non-neoplastic surgical tissue specimens by using specific antibodies in immunoblots and by RT-PCR mRNA analysis. The presence of CYP1A, 2E1, 3A and 4A enzymes was demonstrated by both techniques; CYP2A reactive protein was also detected by immunoblot. The presence of CYP4B1 mRNA was established but no specific antibody was available for detection of the corresponding protein by immunoblot. CYP2B6/7 mRNA was not detected in any sample. The mRNA transcripts for CYP1A1, 2E1, 4A11 and 4B1 were consistently detected in the majority of samples (>84%), whereas CYP1A2 mRNA was only detected in 11 of 19 specimens examined. An RT-PCR method to differentiate CYP3A4 and 3A5 mRNA was developed. This demonstrated CYP3A5 mRNA expression in all samples tested, whereas CYP3A4 mRNA was not detectable, suggesting that CYP3A5 is the major CYP3A protein in human oesophagus. There were significant interindividual variations in the amount of proteins, ranging from 8-fold for CYP4A to 43-fold for CYP2E1. For each patient, data on exposure to risk factors for oesophageal cancer were available, including tobacco smoke, alcohol, gastro-oesophageal reflux and hot beverage consumption. None of these risk factors or other patient characteristics (age, sex, tumour location and tumour stage) were correlated with the protein level of the individual CYP enzymes as determined by quantitation of immunoblot staining. However, the small series of samples precludes any strong conclusion concerning the lack of such correlations. There were no differences between squamous cell carcinomas and adenocarcinomas in either the qualitative or quantitative expression of the CYP enzymes. These data demonstrate that a range of CYP enzymes are expressed in human oesophageal mucosa and indicate that this tissue has the capacity to activate chemical carcinogens to reactive DNA binding metabolites.

Adult↗
PubMed1998

Sequential changes in cadherin-catenin expression associated with the progression and heterogeneity of primary oesophageal squamous carcinoma.

Maintenance of an adhesive function for cadherins requires appropriate membranous cellular expression and intact cadherin-catenin complexes. In normal squamous mucosa of the oesophagus there is membranous co-expression of E- and P-cadherin (E-cad, P-cad) in the basal compartment, whereas suprabasal stratification is associated with preservation of E-cad expression but loss of P-cad. Immunohistochemical staining of squamous dysplasia/carcinoma in situ shows a striking increase in the proportion of cells within the epithelial compartment showing co-expression of E- and P-cad with strong appropriate membranous expression of beta and gamma catenin. Strong membranous co-expression of E- and P-cad and beta catenin is seen on keratinocytes at the periphery of islands of invasive better-differentiated squamous carcinoma with keratinisation, mimicking normal mucosa. Beta catenin may be phosphorylated with implied loss of cadherin binding. Membranous cadherin and catenin expression is significantly down-regulated in poorly differentiated squamous carcinoma. No beta catenin mutations were demonstrated in squamous carcinomas following DNA extraction and sequencing, nor was any nuclear cadherin seen. Changes in cadherin-catenin complexes with cellular phenotype is well demonstrated in spindle cell carcinomas with a shift of cadherin expression from membranous to cytoplasmic between the epithelioid and spindle cell components of the tumour and with loss of expression in the sarcomatoid elements. In conclusion, we demonstrate an increased expression of P-cadherin early in tumourigenesis with loss of cadherin-catenin complexes in poorly differentiated invasive carcinomas. Cadherin/catenin expression may govern both the phenotype and biology of oesophageal squamous carcinomas.

Cadherins↗
PubMed1998

Distinct regions of frequent loss of heterozygosity of chromosome 5p and 5q in human esophageal cancer.

Loss of heterozygosity (LOH) studies reported thus far suggest that tumor suppressor loci on chromosome 5q are important in esophageal cancer (EC) while little is known about the involvement of chromosome 5p. To investigate the potential existence of tumor suppressor gene(s) on chromosome 5 contributing to the development of EC, we performed LOH studies using a total of 24 polymorphic markers spanning the entire chromosome 5. Seventy primary esophageal cancers were microdissected and allelic deletions were detected by polymerase chain reaction (PCR)-single strand conformation polymorphism or by microsatellite analysis. LOH was observed in at least 1 of the loci in 47 of 70 (67%) esophageal tumors. Initially, 40 tumors [24 squamous cell carcinomas (SCC) and 16 adenocarcinomas (ADC)], each with matched histologically normal esophageal mucosa, were analyzed at 15 marker loci on 5p and 5q. A novel locus, D5S667 on 5p15.2, exhibited the highest frequency of LOH (44%) in these tumors along with another previously reported region of frequent deletion, irf-1 (5q31.1). In a series of 30 additional EC tumors (11 SCC and 19 ADC), a detailed LOH analysis of chromosome 5p15.2 region was conducted using 10 additional polymorphic markers, which mapped the frequently deleted region within 1 cM. Overall, LOH at the D5S667 locus was observed more frequently in SCC than in ADC (62% vs. 23%, p = 0.01). This significant rate of LOH of a distinct region of chromosome 5p implicates the existence of a putative tumor suppressor gene locus involved in EC.

Adenocarcinoma↗
PubMed1998

A phase II trial of preoperative mitomycin, cisplatin and 5-fluorouracil in adenocarcinoma of the oesophagus.

The effect of neoadjuvant chemotherapy in patients with apparently operable adenocarcinoma of the oesophagus has been investigated. Two courses of mitomycin, cisplatin and 5-fluorouracil (MCF) were given, followed by a radiological evaluation of response. Twenty-two of 25 patients completed both courses. Two showed a complete response and 12 a partial response. There was a pathological complete response of the primary tumour in only one patient (although there was residual secondary tumour in a local lymph node). The main toxicity was myelosuppression, with 9/22 patients having the second chemotherapy course delayed. There were three sudden deaths, one due to a pulmonary embolus and two due to complications of infections. Twenty-one patients underwent surgical exploration; there were 18 resections. Although the radiological response rate of MCF (14/25; 56%; 95% CI 37-75) appeared promising, there were no pathological complete responders. Further Phase II trials are needed to identify more efficacious agents and regimens that will yield a pathological response rate of at least 10%, before proceeding to randomized trials of neoadjuvant chemotherapy for adenocarcinoma of the oesophagus.

Adenocarcinoma↗
PubMed1998

p53 alterations in oesophageal cancer: association with clinicopathological features, risk factors, and survival.

AIM: To characterise the spectrum of p53 alterations (gene mutations and protein accumulation) in a consecutive series of surgically resected oesophageal cancers, and to evaluate associations with clinicopathological findings (age, sex, tumour histology, grade, and stage), potential risk factors (alcohol, tobacco, hot beverage consumption, history of gastrooesophageal reflux disease and antacid use), and survival. METHODS: The case series comprised 61 sequentially accrued patients with primary oesophageal carcinomas. Genomic DNA was extracted from banked (frozen) tumours and matched normal mucosal tissue; p53 mutations (exons 4-10) were studied by means of polymerase chain reaction (PCR)/single strand conformation polymorphism (SSCP) analysis and DNA sequencing. Immunohistochemistry (DO7, CM1) was used to assess cell nuclear p53 protein accumulation. Risk factor data, overall and disease free survival were measured prospectively, and analysis was carried out at the univariate level using Kaplan-Meier survival curves with log rank tests, and in multivariate analysis using Cox's proportional hazards models (parsimonious and fully adjusted). RESULTS: p53 mutations were found in 59% (36 of 61) and p53 protein accumulation was detected in 39% (24 of 61) of oesophageal cancers. Eighty eight per cent (23 of 26) of poorly differentiated tumours had p53 alterations compared with 57% (20 of 35) of moderate/well differentiated tumours (odds ratio (OR) = 5.575; p = 0.013). p53 mutations increased significantly with increasing consumption of hot beverages (measured by the average temperature of beverage, number consumed daily, and an index made by multiplying the two variables together) using both univariate (OR = 18.6; p = 0.0025) and multivariate (OR = 24.5; p = 0.0025) analysis. p53 alterations were associated with reduced disease free and overall survival (p = 0.051, log rank), with a univariate (unadjusted) hazard ratio (HR) of 2.241 (95% confidence limits (CL) = 0.973, 5.159; p = 0.058) for overall survival. By multivariate analysis adjusted for other relevant variables, the HR for tumours with p53 alterations was estimated at 2.913 (95% CL = 1.069, 7.936; p = 0.036) for overall survival. CONCLUSIONS: This study reports novel p53 mutations (exon 10), and an association between increasing consumption of hot beverages as a risk factor for p53 mediated oesophageal cancer. p53 is a potentially useful prognostic marker in this disease.

Adult↗
PubMed1997

ras mutation and expression of the ras-regulated genes osteopontin and cathepsin L in human esophageal cancer.

As part of our ongoing studies to characterize molecular alterations in a well-defined series of surgically resected esophageal cancers, we examined the expression of 2 ras-regulated genes, whose products (osteopontin and cathepsin L) previously were shown to be associated with tumor invasion and metastasis. RNA was extracted from primary esophageal tumors (adenocarcinomas, 19; squamous-cell carcinomas, 6) and matched histologically normal esophageal mucosa from the distant resection margin. Northern analysis was used to quantitate RNA, relative to an 18S rRNA control, and immunohistochemistry to assess the tissue distribution of osteopontin. In addition, H-, K- and N-ras mutations were studied in the same tissues using PCR and hybridization with allele (mutant)-specific oligonucleotide probes. We demonstrated a K-ras mutation (codon 12, GTT) in one esophageal adenocarcinoma. The ras-regulated gene osteopontin was over-expressed in 100% of squamous-cell carcinomas and in 58% of adenocarcinomas relative to matched normal esophageal mucosa. Patterns of immunoreactivity for osteopontin protein also varied between squamous-cell carcinomas (tumor cell staining) and adenocarcinomas (predominantly tumor-infiltrating macrophages). Expression of cathepsin L also varied with esophageal tumor histology, with over-expression in 58% of primary esophageal adenocarcinomas and 33% of squamous-cell cancers.

Adenocarcinoma↗
PubMed1997

Flow cytometry in squamous cell esophageal cancer and precancerous lesions.

Flow cytometry has also been used to study the nuclear DNA content (ploidy) and cell cycle kinetics of esophageal cancers. Studies of limited numbers of patients with Barrett's esophagus undergoing endoscopic surveillance suggested that aneuploidy may be a useful marker to identify subsets of patients at increased risk for malignancy. Few studies to date have evaluated premalignant tissues associated with the development of squamous-cell cancer of the esophagus. The present retrospective study comprises 80 surgical specimens of squamous-cell carcinoma of the esophagus from a high-incidence region of Thailand. All patients had surgery at the Department of Surgery, Prince of Songkla University, between March 1983 and December 1993. Sets of serial sections were cut every 0.5 cm starting from the proximal margin and down to the distal margin, and histopathology was confirmed to flow cytometric parameters (DNA content, S-phase fraction). Aneuploidy was found in 84% of squamous-cell carcinoma, 22.2% of carcinoma in situ, 28.6% of severe dysplasia, 11.0% of moderate dysplasia and 0% of mild dysplasia and normal esophageal mucosa specimens. The percentage was higher according to the level of severity or dysplasia. S-phase fraction was found to be 21.0 +/- 0.9% in squamous-cell carcinoma, 20.3 +/- 10.3% of carcinoma in situ, 20.9 +/- 5.3% of severe dysplasia, 12.9 +/- 9.7% of moderate dysplasia 7.6 +/- 0.8% of mild dysplasia and 8.9 +/- 3.2% of normal tissue. Similarly, the percentage of S-phase fraction tends to be higher according to the level of severity or dysplasia. These findings demonstrate that the aneuploidy and percentage of S-phase fraction tend to correlate with progression of esophageal premalignant tissues to invasive carcinoma. These measures may be clinically useful to identify patients at increased risk for esophageal malignancy.

Aged↗
PubMed1997

Radiologic placement of metallic esophageal stents: preliminary experience.

OBJECTIVE: To assess the usefulness of covered, self-expanding metallic stents for alleviating stricture associated with malignant esophageal lesions. PATIENTS AND METHODS: Self-expanding metallic stents were placed in 10 patients with dysphagia related to stricture caused by malignant esophageal lesions. The stents were placed fluoroscopically with local anesthesia, and patency of the esophageal lumen was assessed by barium study after the procedure. The patients were then followed clinically. RESULTS: In all 10 cases patency of the lumen was renewed after stent placement. After the procedure 9 of the patients could tolerate a normal or near-normal diet; in the other patient esophageal perforation occurred, and clinical deterioration prevented oral intake of food. In one patient, 2 stents were needed because of the length of the stricture. Two patients experienced reflux after placement of the stent across the gastro-esophageal junction. Another patient had asymptomatic aspiration after stent placement in the proximal esophagus. In 2 patients, symptoms associated with tracheoesophageal fistula were relieved after placement of the stents. Six of the 10 patients died; mean survival after the procedure was 12 (range 1 to 56) weeks. The other 4 patients were alive at the time of writing, having survived for a mean of 7.5 (range 2 to 13) weeks; all of these patients tolerated a near-normal diet. CONCLUSIONS: The placement of covered, self-expanding metallic stents is a quick, effective method of palliating dysphagia related to stricture caused by malignant esophageal lesions.

Aged↗
PubMed1996

Osteopontin expression in lung cancer.

Osteopontin (OPN), an integrin-binding, transformation-associated protein, is secreted by tumor cell lines in culture and is associated with increased malignancy in some experimental tumor systems. Little is known, however, about the significance of OPN expression in human cancers. The aims of this study were to determine if OPN was expressed in a series of surgically resected lung cancers, and if there was a relationship between OPN expression and clinico-pathologic findings or outcome. Twenty-five patients who underwent curative pulmonary resection were studied prospectively. RNA was extracted from primary tumor and distant normal lung tissue for each patient. OPN RNA levels were evaluated by northern blotting. Immunohistochemistry on paraffin-embedded tissue, using an anti-OPN monoclonal antibody, was performed to assess tissue distribution of OPN protein. OPN RNA and protein were over-expressed in the majority of tumors, relative to paired normal tissue. There was variation in the cells of the tumor that were OPN-immunopositive. In some cases OPN was present in tumor cells, while in the majority of cases OPN was detected primarily in tumor-infiltrating macrophages and necrotic areas. Over-expression of OPN RNA or protein generally was not related to clinico-pathological findings. However, there was a statistically significant association between OPN-immunopositivity in the tumor and patient survival. These findings suggest that OPN levels in lung tumors have the potential to provide clinically important predictive information on patient outcome, and that OPN may play a role in the biology of lung cancer.

Adult↗
PubMed1996

Mutations of p53 in Barrett's esophagus and Barrett's cancer: a prospective study of ninety-eight cases.

We had previously identified p53 mutations in Barrett's esophagus and therefore began a multiinstitutional study to determine their significance as a marker for malignancy. Ninety-eight patients from four institutions were studied. Forty-eight patients (37 men and 11 women, mean age 56.2 years) had Barrett's esophagus with metaplasia or dysplasia but no evidence of malignancy at a mean follow-up of 2.2 years. Barrett's esophagus was classified as metaplasia with no evidence of dysplasia in 32 patients, as low-grade dysplasia in 13, and as high-grade dysplasia in three. The other 50 patients (46 men and four women, mean age 60.2 years) had adenocarcinoma arising in Barrett's esophagus. Tissues from normal stomach or esophagus, tumor, and Barrett's esophagus were obtained for deoxyribonucleic acid analysis by endoscopic biopsy from patients with Barrett's esophagus or cancer or during operations on some patients with Barrett's cancer. Exons 5 through 9 of the p53 gene were studied for mutations by single-strand conformational polymorphism analysis after polymerase chain reaction amplification. Mutations detected by single-strand conformational polymorphism analysis were confirmed by deoxyribonucleic acid sequencing. None of the tissue samples from patients with Barrett's esophagus alone and no dysplasia or low-grade dysplasia had any p53 mutations, but one of the three patients with high-grade dysplasia and no evidence of invasive malignancy did have a p53 mutation. Of the 50 patients with Barrett's cancer, however, 23 (46%) had p53 mutations in Barrett's epithelium, tumors, or both. Twenty of these patients had p53 mutations in the tumor only (n = 16) or in both tumor and Barrett's epithelium (n = 4), suggesting that the mutation plays a direct role in carcinogenesis. Mutations in Barrett's epithelium were found in one patient in the group without malignancy and in seven patients with cancer (one with no dysplasia, two with low-grade dysplasia, and five with high-grade dysplasia). In three patients with cancer, mutations occurred only in Barrett's epithelium, suggesting that such mutations may also be a marker for genomic instability. Mutations were predominantly found in exons 5, 7, and 8, and transitions from guanine to adenine were the most frequent changes. Mutations of p53 are clearly involved in the pathogenesis of Barrett's cancer for a subset of patients (46%), and the fact that we could detect mutations in premalignant Barrett's epithelium supports the hypothesis that p53 mutations may be a useful marker for patients at increased risk for development of invasive cancer.

Adenocarcinoma↗
PubMed1996

Dysphagia lusoria: extrathoracic surgical management.

OBJECTIVE: To report a case of dysphagia lusoria managed by an extrathoracic approach. DESIGN: Case report and literature review. SETTING: A university hospital. PATIENT: A 39-year-old man, who presented with weight loss and dysphagia. Aortography and computed tomography revealed an aberrant subclavian artery compressing the esophagus against the aortic arch. INTERVENTION: The right subclavian artery was divided at its origin and reimplanted onto the right carotid artery. The operation was performed through a right supraclavicular incision without opening the chest. RESULTS: There was no operative morbidity. Six months postoperatively the patient was asymptomatic and had gained weight. There was no radiologic evidence of esophageal compression. CONCLUSIONS: Based on the results of our case of dysphagia lusoria and the reports of others that have started to appear in the literature, consideration should be given to repairing a symptomatic, nonaneurysmal aberrant right subclavian artery through an extrathoracic approach.

Adult↗
PubMed1995

Prognostic value of DNA index, S-phase fraction and p53 protein accumulation after surgical resection of esophageal squamous-cell carcinomas in Thailand.

The prognostic value of cell nuclear DNA content, S-phase fraction and p53 protein accumulation in esophageal squamous-cell carcinomas was studied in a consecutive series of 80 patients from a high-incidence region of southern Thailand, who underwent esophagectomy between 1983 and 1993. Flow cytometry was used to determine tumor ploidy, DNA index and S-phase fraction, while p53 protein accumulation was evaluated immunohistochemically using the monoclonal anti-p53 antibody, CO7. Biomarkers were correlated with clinico-pathologic findings and survival by univariate and multivariate analysis. p53 protein was found in 40 tumors (50%), and was associated with significantly reduced overall survival. In patients with immunopositive tumors, depth of primary tumor invasion, lymph-node status. TNM stage and tumor grade were also significant prognostic factors. Additional predictors of reduced overall survival after esophagectomy, determined by flow cytometry, included S-phase fraction above 10%, aneuploidy (DNA index 1.2-1.8) and multiploidy (DNA index > 2.2). This study further implicates p53 in the pathogenesis of esophageal squamous-cell carcinoma. Prognostic factors such as p53 protein, S-phase fraction and DNA index may be useful in stratifying patients for adjuvant therapies in future clinical trials of esophageal cancer.

Adult↗