Purpose: Follicular lymphoma, the most common indolent lymphoma, is clinically heterogeneous. CDKN2A encodes the tumor suppressors p16INK4a and p14 ARF and frequently suffers deleterious alterations in cancer. We investigated the hypothesis that deletion or hypermethylation of CDKN2A might identify follicular lymphoma cases with distinct clinical or pathologic features potentially amenable to tailored clinical management. Experimental Design: Deletion of CDKN2A was detected in pretreatment biopsy specimens using a single nucleotide polymorphism-based approach or endpoint PCR, and methylation of CpG elements in CDKN2A was quantified by methylation-specific PCR. Correlations between CDKN2A status and pathologic or clinical characteristics, including overall survival (OS), were investigated in 106 cases using standard statistical methods.Results: Deletion of CDKN2A was detected in 9 of 111 samples (8%) and methylation was detectable in 22 of 113 (19%). CDKN2A was either deleted or methylated in 29 of 106 cases (27%) and this status was associated with inferior OS especially among patients treated with rituximab (P ¼ 0.004). CDKN2A deletion or methylation was associated with more advanced age (P ¼ 0.012) and normal hemoglobin (P ¼ 0.05) but not with sex, FLIPI score, ECOG stage, LDH, performance status, number of involved nodal sites, B symptoms, histologic grade, the presence of a component of diffuse large B-cell lymphoma, proliferation index, or other pathologic factors.Conclusions: Our results show that deletion or methylation of CDKN2A is relatively common in pretreatment follicular lymphoma biopsy specimens and defines a group of cases associated with reduced survival in the rituximab era presumably on the basis of more aggressive disease biology. Clin Cancer Res; 20(6); 1676-86. Ó2014 AACR.

Recombinant interleukin-21 (IL-21) has potential utility in cancer therapy. Stimulation with IL-21 can induce apoptosis in follicular lymphoma (FL) cells, and existing studies have suggested that IL-21 signaling may function in tumor suppression. In order to elucidate the relationship between IL-21 receptor (IL-21R) expression and clinical and pathological features in FL, IL-21R was quantified in 114 pretreatment biopsy samples using either conventional immunohistochemistry or immunofluorescence microscopy and automated quantitative analysis (AQUA). Reduced expression of IL-21R was associated with favorable overall survival (p = 0.048). AQUA analysis showed an association with the presence of diffuse large B-cell lymphoma (DLBCL) in the biopsy sample (p = 0.03), and expression of IL-21R was up-regulated upon transformation of FL to DLBCL in two cases. Our results based on the largest survey to date raise the possibility that IL-21 signaling in FL cells, rather than being tumor suppressive, supports tumor progression and that therapeutic benefit could be realized by blocking IL-21R instead of stimulating it.

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Australia/New Zealand (ASR 36.4 and 27.7 per 100,000 for males and females respectively). The incidence of CRC tends to be low in most regions of Western Africa (ASR 7.0 and 5.1 per 100,000 for males and females respectively), and in South Central Asia (ASR 6.2 and 4.0 per 100,000 for males and females respectively) (Sung et al., 2021). In general, the incidence of CRC in high/very high Human Development Index (HDI) countries is higher (ASR 29.0 and 7.4 per 100,000 for males and females respectively) than in the low-and middle HDI countries (ASR 20.0 and 5.4 per 100,000 for males and females respectively) (Sung et al., 2021;Arnold et al., 2020).According to Saudi cancer incidence report in 2018, CRC is the most common cancer among men (15.3%) and third among women (9.8%) (Table 1