Clinicopathological Variables Associated with Lymph Node Metastasis and Prognostic Factors in pT2 Gastric Cancer

The Journal of International Medical Research 2009; 37: 359 – 366 Clinicopathological Variables Associated with Lymph Node Metastasis and Prognostic Factors in pT2 Gastric Cancer A WANG1, P GUO2, Z SUN2 AND H XU2 1 Department of Nursing, and 2Department of Surgical Oncology, First Affiliated Hospital of the Chinese Medical University, Heping, Shenyang, China This retrospective study investigated the clinicopathological variables associated with lymph node metastasis and prognosis in 325 patients with pT2 gastric cancer in order to set out a foundation for the surgical management of this condition. Univariate and multivariate analyses identified factors that were predictive of lymph node metastasis. Cox regression analysis evaluated the effect of prognostic factors on survival. Tumour location, maximum tumour diameter, lymphatic invasion and total retrieved lymph nodes (tLN) were revealed as independent factors for lymph node metastasis in pT2a gastric cancer, whereas histological type, lymphatic invasion and tLN were associated with lymph node metastasis in patients with pT2b gastric cancer. Maximum tumour diameter, lymphatic invasion and metastatic lymph node (mLN) ratio, but not tLN, were independent prognostic factors in pT2a cancer. Maximum tumour diameter and mLN ratio, but not tLN, were independent prognostic factors in pT2b cancer. Overall, it is concluded that maximum tumour diameter and mLN ratio are important prognostic factors in pT2 gastric cancer. KEY WORDS: GASTRIC CANCER; CHINESE PATIENTS; PT2 CATEGORY; METASTATIC LYMPH NODE RATIO; TUMOUR DIAMETER; PROGNOSTIC FACTORS; SURVIVAL Introduction The survival of patients with gastric cancer has recently been improved because of early detection, rational lymphadenectomy and several therapeutic modalities.1 – 3 Gastric cancer is, however, still a major cause of cancer deaths worldwide.4,5 Patients with T1 (invading the mucosa or submucosa) gastric cancer have a good prognosis and their 5year survival rate is > 90%.5 In contrast, patients with T3 (invading the serosal layer) gastric cancer have a poor prognosis and their 5-year survival rate after resection is about 30%.6 T2 gastric cancer is considered to be intermediate between early gastric cancer and T3 in terms of prognosis.7 Therefore, a better evaluation of the factors influencing outcome could be useful in planning the most appropriate therapeutic strategy to use in patients with gastric cancer. The former tumour, node, metastases 359 A Wang, P Guo, Z Sun et al. Lymph node metastasis and prognostic factors in pT2 gastric cancer (TNM) classification of malignant tumours defined the pT2 designation for primary tumours that had invaded the muscularis propria or the subserosa.7 In 2002, however, the American Joint Committee on Cancer (AJCC) further divided pT2 gastric adenocarcinomas into type pT2a (invasion of the muscularis propria) and type pT2b (invasion of the subserosa).8 At present, reports on the prognostic factors associated with this sub-classification of pT2 gastric cancers are still sparse.9 – 11 Moreover, a few studies carried out in Western countries have suggested that mLN ratio is a reliable prognostic factor,12 – 15 but relevant data are virtually absent for patients in China. This study was designed to investigate both the clinicopathological and prognostic factors, in particular the mLN ratio, which might improve the evaluation of pT2 gastric cancer in Chinese patients. Patients and methods PATIENTS This was a retrospective study that selected gastric cancer patients with pT2 tumours, who had undergone radical operation at the First Affiliated Hospital of the Chinese Medical University (Shenyang, China) between 1980 and 2002. Selection criteria for inclusion were: (i) curative operations had been performed;16 (ii) > 15 lymph nodes had been resected and the resected specimens had been pathologically examined;8 and (iii) the patient’s medical records were complete. More than one pathologist was involved in corroborating the histological diagnosis, post-operatively, for all cases. All the slides were also re-examined by one of the authors and another pathologist in order to confirm the sub-classification of the pT2 gastric cancers for all cases. The study protocol was approved by the Ethics Committee of the Chinese Medical University. CLASSIFICATIONS AND SUBCLASSIFICATIONS OF GASTRIC CANCER The pT2 and pN categories of tumours were defined according to the 5th edition of the UICC staging system: pN0, no mLNs; pN1, 1 – 6 mLNs; pN2, 7 – 15 mLNs; and pN3, > 15 mLNs).7 The location of the tumour, the gross morphological type (Bormann) and the histological type of the tumour, and the classification of the lymph nodes were as referred to in the Japanese Gastric Cancer Association classification.15 The mLN ratio was categorized into four different grades: 0, < 40%, 40 – 79% and ≥ 80%.3 STATISTICAL ANALYSIS All data were analysed using SPSS® statistics software (version 13.0, SPSS Inc., Chicago, IL, USA). The χ2 test and independent t-tests were used to compare the clinicopathological factors of patients with pT2a and pT2b gastric cancers. Disease-specific survival was analysed using the Kaplan–Meier method. The log-rank test was used to analyse survival differences. Multivariate analyses were performed using the Cox proportional hazards model selected in a forward stepwise manner. A P-value of < 0.05 was considered to be statistically significant. Results DEMOGRAPHICS AND CLINICOPATHOLOGICAL CHARACTERISTICS In this retrospective study, 325 patients with pT2 gastric tumours were selected from a total of 2322 patients with gastric cancer on whom a radical operation had been performed. Of the study group, 242 patients had pT2a and 83 patients had pT2b cancers. The male-tofemale ratio among the 325 enrolled patients was 2.92:1 and the mean age was 57.32 years 360 A Wang, P Guo, Z Sun et al. Lymph node metastasis and prognostic factors in pT2 gastric cancer (range 24 – 80 years). Lymph node dissection of D2 or greater was performed in all patients and the mean number of examined lymph nodes was 17.16. Patients with pT2a and pT2b tumours were similar with regard to age and gender distribution, total number of retrieved lymph nodes (tLN), histological type and pathological lymph node status. The pT2b tumours were significantly larger, more frequently located in the entire or upper third of the stomach, more likely to be Bormann III and IV tumours, and more likely to be associated with lymphatic vessel invasion than the pT2a tumours (P ≤ 0.012) (Table 1). TABLE 1: Demographic, clinical and pathological characteristics of patients with pT2 gastric cancer (n = 325) Gastric pT2 tumour sub-group Variable Mean age (years) Gender ratio n (%) Male (n = 242) Female (n = 83) Mean number of tLN Tumour focus number, n (%) Single (n = 308) Multiple (n = 17) Tumour location, n (%) Upper stomach (n = 37) Middle stomach (n = 45) Lower stomach (n = 23 (...truncated)