Immunohistochemical overexpression of BCL-2 protein predicts an inferior survival in patients with primary central nervous system diffuse large B-cell lymphoma

Abstract

This study was designed to analyze the clinical characteristics and prognostic value of c-MYC and BCL-2 proteins expression in patients with primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL).82 patients newly diagnosed with PCNS-DLBCL, from January 2008 to November 2018, were enrolled in this study. Clinical characteristics, immunohistochemical features, laboratory examinations, and treatment outcome were analyzed among these patients.Among these 82 cases, 45 were males (54.9%) and 37 were females (45.1%). Age ranged from 16 to 78 years old, and 29 patients (35.4%) were elder than 60 years old, with median age at 57 years old. According to Hans classification, 25 were accounted for origin of germinal center B-cell (GCB) subtype (30.5%) and 49 were accounted for non-GCB subtype (59.8%), respectively. Eight patients were unclassified due to lack of detailed pathological results. The median survival of these 82 patients was 30 months, and 1-year, 3-year, and 5-year overall survival (OS) rate was 59.7%, 44.6%, and 34.1%, respectively. Patients treated with sequential HD-MTX based chemotherapies showed a superior prognosis than those without. In combination with rituximab, the outcome was further improved. The median OS was 55 months in HD-MTX + R group, 27 months in HD-MTX group, and 9 months in other groups, respectively. Univariate analysis identified age ≥60, ECOG score ≥ 2 points, and overexpression of BCL-2 protein (≥85%) were adverse prognostic factors for OS. Co-expression of c-MYC (≥40%) and BCL-2 (≥50%) proteins was associated with poor ECOG score, high Ki-67 expression, and trended towards an inferior outcome. Gender, lesion location, number of lesions, lactic dehydrogenase (LDH), cell of origin, BCL-6 protein expression, expression of c-MYC protein alone and Ki-67 ≥85% had no significant impact on OS.In patients with PCNS-DLBCL, age ≥60 years old, ECOG score ≥2 points, and overexpression of BCL-2 protein (≥85%) were associated with a poor survival. HD-MTX based chemotherapies in combination with rituximab could improve the prognosis.

Sinonasal DLBCL: molecular profiling identifies subtypes with distinctive prognosis and targetable genetic features

“… 32 Interestingly, double expression and concurrent BCL6 overexpression is frequently observed in extranodal lymphomas, including primary CNS DLBCL (∼80%) and primary cutaneous DLBCL (leg type) (∼70%). 11 , 12 , 13 , 24 , 33 , 34 , 35 Our analysis revealed a high incidence of double expression in the ABC subtype: 77% (52/68) vs 18% (8/44) in the GCB subtype ( P < .001) and high rates of BCL6 overexpression in both subtypes, 77% in ABC subtype vs 88% in GCB subtype ( Figure 1 ).…”

A genetically distinct pediatric subtype of primary CNS large B-cell lymphoma is associated with favorable clinical outcome

“…Four tumors in this group exhibited a small number of chromosomal gains/losses (<5/tumor), while the quantity of chromosomal aberrations was high (5+) in the remaining 4 tumors. No differences in radiologic or histologic features between these pediatric type PCNS-LBCL and their adult type counterparts was appreciable (Figure 2A-F Kaplan-Meier survival analysis demonstrated a 5-year overall survival (OS) of 100% for the pediatric type, MYD88-wildtype group, which was substantially longer than PCNS-LBCL in adult patients from previous studies [15][16][17][18][19][20] (Figure 2G, Sup. Tables 8-9).…”

Knockdown of the long non‑coding RNA CACNA1G‑AS1 enhances cytotoxicity and apoptosis of human diffuse large B cell lymphoma by regulating miR‑3160‑5p

“…A previous study revealed that Bcl-2, as one of the vital apoptosis suppressor genes, can effectively regulate the development and differentiation of normal B cells ( 40 ). High expression levels of Bcl-2 were reported in ~45% of patients with DLBCL ( 41 ). In addition, patients with DLBCL and high expression levels of Bcl-2 have a significantly worse prognosis with R-CHOP treatment ( 42 ).…”