Unnecessity of lymph node regression evaluation for predicting gastric adenocarcinoma outcome after neoadjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy has been applied worldwide to improve the survival of patients with gastric adenocarcinoma (GAC). The evaluation of histological regression in primary tumors is valuable for predicting prognosis. However, the prognostic effect of regression change in lymph nodes (LNs) remains unclear. AIM: To confirm whether the evaluation of regression change in LNs could predict the prognosis of GAC patients who received neoadjuvant chemotherapy followed by surgery. METHODS: In this study, we evaluated the histological regression of resected LNs from 192 GAC patients (including those with esophagogastric junction adenocarcinoma) treated with neoadjuvant chemotherapy. We classified regression change and residual tumor in LNs into four groups: (A) true negative LNs with no evidence of a preoperative therapy effect, (B) no residual metastasis but the presence of regression change in LNs, (C) residual metastasis with regression change in LNs, and (D) metastasis with minimal or no regression change in LNs. Correlations between regression change and residual tumor groups in LNs and regression change in the primary tumor, as well as correlations between regression change in LNs and clinicopathological characteristics, were analyzed. The prognostic effect of regression change and residual tumor groups in LNs was also analyzed. RESULTS: We found that regression change and residual tumor groups in LNs were significantly correlated with regression change in the primary tumor, tumor differentiation, ypT stage, ypN stage, ypTNM stage, lymph-vascular invasion, perineural invasion and R0 resection status. Regression change and residual tumor groups in LNs were statistically significant using univariate Cox proportional hazards analysis, but were not independent predictors. For patients who had no residual tumor in LNs, the 5-year overall survival (OS) rates were 67.5% in Group A and 67.4% in Group B. For the patients who had residual tumors in LNs, the 5-year OS rates were 28.2% in Group C and 39.5% in Group D. The patients in Groups A+B had a significantly better outcome than the patients in Groups C+D (P < 0.01). No significant differences in survival were found between Groups A and B, or between Groups C and D. CONCLUSION: The existence of residual tumor in LNs, rather than regression change in LNs, is useful for predicting the prognosis after neoadjuvant chemotherapy in GAC patients. In practice, it may not be necessary to report regression change in LNs.

Clinicopathological parameters predicting recurrence of pT1N0 esophageal squamous cell carcinoma.

AIM: To identify the clinicopathological characteristics of pT1N0 esophageal squamous cell carcinoma (ESCC) that are associated with tumor recurrence. METHODS: We reviewed 216 pT1N0 thoracic ESCC cases who underwent esophagectomy and thoracoabdominal two-field lymphadenectomy without preoperative chemoradiotherapy. After excluding those cases with clinical follow-up recorded fewer than 3 mo and those who died within 3 mo of surgery, we included 199 cases in the current analysis. Overall survival and recurrence-free survival were assessed by the Kaplan-Meier method, and clinicopathological characteristics associated with any recurrence or distant recurrence were evaluated using univariate and multivariate Cox proportional hazards models. Early recurrence (≤ 24 mo) and correlated parameters were assessed using univariate and multivariate logistic regression models. RESULTS: Forty-seven (24%) patients had a recurrence at 3 to 178 (median, 33) mo. The 5-year recurrence-free survival rate was 80.7%. None of 13 asymptomatic cases had a recurrence. Preoperative clinical symptoms, upper thoracic location, ulcerative or intraluminal mass macroscopic tumor type, tumor invasion depth level, basaloid histology, angiolymphatic invasion, tumor thickness, submucosal invasion thickness, diameter of the largest single tongue of invasion, and complete negative aberrant p53 expression were significantly related to tumor recurrence and/or recurrence-free survival. Upper thoracic tumor location, angiolymphatic invasion, and submucosal invasion thickness were independent predictors of tumor recurrence (Hazard ratios = 3.26, 3.42, and 2.06, P < 0.001, P < 0.001, and P = 0.002, respectively), and a nomogram for predicting recurrence-free survival with these three predictors was constructed. Upper thoracic tumor location and angiolymphatic invasion were independent predictors of distant recurrence. Upper thoracic tumor location, angiolymphatic invasion, submucosal invasion thickness, and diameter of the largest single tongue of invasion were independent predictors of early recurrence. CONCLUSION: These results should be useful for designing optimal individual follow-up and therapy for patients with T1N0 ESCC.

[Clinicopathologic analysis of nodal marginal zone B cell lymphoma].

OBJECTIVE: To investigate the clinicopathologic features of primary nodal marginal zone B-cell lymphoma (NMZL). METHODS: Hematoxylin-Eosin staining and immunohistochemistry were used to evaluate the histological and immunophenotypic characteristics of lymph node (LN) tissue in 22 NMZL cases. Additionally, interphase fluorescence in-situ hybridization (FISH) was carried out to detect the presence of t(11;18) (q21;q21)/API2-MALT1 and/or t(14;18)(q32;q21)/IGH-MALT1 in 9 cases. RESULTS: The median age of the 22 patients was 62 (16 - 77) ys. The male-to-female ratio was 1.2:1. All patients exhibited asymptomatic lymphadenopathy with the cervical region as the most often site to be involved (n = 11), followed by axillary (n = 9), inguinal (n = 7), submandibular (n = 6), mediastinal (n = 4), supraclavicular (n = 2) and retroperitoneal lymph nodes (n = 1). The Ann Arbor stages were I/II in 13 (59%) cases and III/IV in 9 (41%). Immunohistochemical study showed a consistently strong expression of CD20 and an absence in the expression of CD3ε, CD10, CD21, CD23, CyclinD1 and BCL6 by the tumor cells in all the cases. Frequency of expression of CD5 and BCL2 were 39% (7/18) and 30% (3/14) respectively. Among the 9 cases performed with FISH, 2 cases harbored t(14;18)and another 1 case positive for t(11;18) and t(14;18). Complete follow-up data were available for 13 cases. The follow-up time was 6 to 44 months. 3 of them died. 3-year cumulative survival rate was 67%. CONCLUSIONS: NMZL patients are often elderly, which mainly present with multiple lymphadenopathy, rare involvement of extranodal organ and early stage. The diagnosis must be based on a combination of clinicopathologic features, especially those patients detected t(11;18) and/or t(14;18).

[Clinical significance of bcl-2 protein expression and classification algorithm in diffuse large B-cell lymphoma].

OBJECTIVE: To investigate the clinical significance of bcl-2 protein expression and three classification algorithms including Hans model, Chan model and Muris model in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: Two-hundred and thirty-seven cases were collected. Standard two-step EnVision method of immunohistochemical staining was used to assess the expression of Ki-67, CD3, CD45RO, CD20, CD79a, bcl-2, bcl-6, CD10, MUM-1, GCET-1, and FOXP-1. The phenotypic classifications were assessed according to the standard of the three models. RESULTS: The male (131 cases) to female (106 cases) ratio was about 1.24:1, the average age was 52.6 years. Seventy-five cases (31.6%, 75/237) showed primarily lymph node involvement. Gastrointestinal tract (71 cases) was the most commonly involved extra-nodal organ. All cases expressed one or more pan B cell markers such as CD20 (99.1%, 231/233). All patients with complete clinical follow-up data survived from 1 - 120 months. The expression of bcl-2 protein indicated an adverse prognosis (P = 0.019). Two-hundred and thirty cases were classified according to Hans model, with ninety five GCB cases and one-hundred and thirty five non-GCB cases. Survival analysis showed no difference between GCB and non-GCB subtypes (P = 0.102). According to the Chan's algorithm, sixty eight case of one-hundred and eighty one were belong to GCB group, with one-hundred and thirteen non-GCB cases. GCB subtype showed much better prognosis than non-GCB subtype according to survival analysis (P = 0.031). Additionally, bcl-2 protein expression in non-GCB subtype showed the worst survival. In Muris' model, 154 of 218 cases were classified as Group 1, while 64 cases were classified as Group 2. Group 1 showed better prognosis than Group 2 (P < 0.05). CONCLUSIONS: Non-GCB group is the more common type of DLBCL in China. High expression of bcl-2 protein is detected in the non-GCB group. Not all subgroups classified with different classification models indicate different prognosis. Bcl-2 expression combined with Chan's algorithm may be the best tool to predict outcome.

[Clinicopathologic and cytogenetic features of 114 Chinese mantle cell lymphoma cases].

OBJECTIVE: To study the clinicopathologic features, immunotype and cytogenetics of Chinese mantle cell lymphoma (MCL). METHODS: 114 MCL cases were collected from hematopathology lab of department of pathology, Peking University, HSC. Routine HE stain and immune stain were used to investigate the clinicopathologic features and immune type. Breaks of CCND1 and IgH/CCND1 fusion genes were detected by FISH. RESULTS: The ratio of male to female was 3.56:1 (89:25) with the median age of 60 years old (20 - 83 years old). 78 cases (68.42%, 78/114) primarily showed lymph node involvement, including 49 cases (49/78, 62.82%) jugular node involvement; 36 cases (31.58%, 36/114) showed extra-nodal involvement. 23 cases (23/114, 20.18%)showed bone marrow involvement. The expressions of CD3ε, CD20, CD79a, PAX5, CD5, cyclinD1 and Bcl-2 were 0% (0/114), 99.12% (113/114), 96.43% (27/28), 97.56% (40/41), 67.89% (74/109), 100% (114/114) and 94.12% (48/51), respectively. Break of CCND1 gene was found in 20 cases (80%, 20/25), the fusion gene of IgH-CCND1 in 16 cases (80%, 16/20), the break of IgH gene in 9 cases (100%, 9/9)and its fusion gene in 8 cases (88.89%, 8/9). We followed up 75 cases with a period of 2-57 months. The median survival was 40.78 months. The survivals at 1 year, 2 year and 3 year were 84.13% (53/63), 68.09% (32/47) and 37.5% (12/32), respectively. The median survival of group with more than 40% expression of Ki-67 was 36 months, the group with less than 40% expression of Ki67 57 months (P = 0.003). 7 of 13 patients accepted Rituximab plus traditional chemotherapy attained CR, 3 cases PR. 11 of 44 cases accepted traditional chemotherapy attained CR, 9 cases PR (P = 0.052). CONCLUSION: Most of Chinese MCL occurred in older male, multi-lymphadenopathy and bone marrow involvement were common in MCL as a aggressive tumor. High expression of Ki-67 was an adverse prognostic indicator. Rituximab could improve the survival. Change of CCND1 gene was the most common cytogenetic abnormality.

[The clinical significance of a new classification algorithm in Chinese DLBCL cases].

OBJECTIVE: To investigate the clinicopathologic features, pathogenesis, diagnostic criteria and the relationship between different classification models and prognosis in Chinese patients with DLBCL, and try to look for the most appropriate classification model to predict clinical prognosis and therapeutic responses for Chinese patients with DLBCL. METHODS: 181 cases of Chinese DLBCLs diagnosed according to the WHO 2008 classification were collected. Standard two-step Envision method of immunohistochemical staining was used to assess the expressions of CD20, CD3ε, CD79a, CD10, Mum-1, Bcl-6, GCET-1, FOXP1 and Ki-67. The phenotypic classifications were assessed according to the standard of Hans model and Chan model. Data were analyzed by χ(2) test and Life Table survival analysis with the SPSS14.0 statistical package. RESULTS: The ratio of male to female in this cohort was 1.26:1. The median age of all patients was 57 yrs with the average age of 53.5 yrs. Of 61 cases (33.7%) primarily showed lymph node involvement. Gastrointestinal tract as the most involved extra-nodal organ was observed in 43 cases (35.8%). All patients with complete clinical follow-up materials survived from 1 - 120 months. The patients showed a high risk for death in the initial one and half years. Three year survival rate was 49.7% (90/181). Three year survival of 44 cases received R-CHOP (Rituximab, cyclophosphamide, doxorubicin, vincristine, bolus) was 76.9% (20/26), whereas 61.9% (60/97) in 119 cases received CHOP alone, R-CHOP group showed better prognosis (P = 0.017). All cases expressed one or more pan B cell markers, such as CD20 (176/179, 98.3%) and CD79a (62/77, 80.5%). For Hans model, 78 cases were classified as GCB group, while 103 cases as Non-GCB group. The ratio of Non-GCB to GCB was 1.32 without difference on the survival (P > 0.05). For the Chan's algorithm, 68 cases belonged to GCB subgroup, while 113 cases non-GCB subgroup. The ratio of non-GCB to GCB was 1.66. GCB subtype showed much better prognosis than non-GCB subtype according to Life Table survival analysis (P < 0.05). CONCLUSION: The epidemiology and clinicopathologic features of Chinese DLBCLs were similarly with the western cases. Chan's algorithm was a significant tool to predict the cell origin and clinical biology of Chinese DLBCLs.