Community pharmacy-level factors associated with medical and nursing home facility collaboration in Japan.

The aim of this study was to clarify the community pharmacy-level factors related to experiences of and attitudes toward collaboration with medical and nursing home care facilities. We conducted a postal questionnaire survey of all pharmacies in Gifu, Japan, assessing the experiences and attitudes of supervising pharmacists regarding the following activities related to collaboration between medical facilities and nursing home care facilities: regional care meetings/service adjustment meetings, case discussion conferences, joint workshops/continuing education conferences, community service, information sharing through medical cooperation networks, and pharmacists accompanying physicians on home care visits. The factors significantly related to inter-professional collaboration were the family pharmacist guidance fee and the number of patients offered pharmaceutical care through cooperation with other medical facilities. Items on attitudes toward collaborating with other medical facilities showed similar results. Overall, policies that support inter-professional collaboration to create a foundation, establish mechanisms to facilitate collaboration, and identify collaborative activities that can be carried out at each pharmacy should be developed.

Color change in Perlodel® tablets induced by LED lighting - photolysis of bromocriptine mesylate.

Various types of fluorescent lights are found in the dispensing rooms of medical facilities, such as hospitals and pharmacies, in Japan. However, to reduce electric power consumption, it was necessary to evaluate the substitution of fluorescent lighting with light emitting diode (LED) lighting, which has become widespread in recent years. We subjectively evaluated several types of medicines stored under various light sources and found that different color changes were induced in tablets. In this study, we focused on Perlodel ® tablets, containing 2.5 mg bromocriptine mesylate, as an example for the objective evaluation of the differences in the color change of tablets when stored under LED lighting and fluorescent lighting. High-performance liquid chromatography (HPLC) analysis of part of the tablet surface area revealed a change from white to light brown or dark brown after 28 days of irradiation, with a residual concentration of bromocriptine mesylate of 85.5 % under fluorescent lighting, 85.6 % under daylight-color LED lighting, 90.3 % under bulb-color LED lighting, and 99.2 % in the dark. In addition, the ultraviolet (UV)-visible spectral study of the absorbance of a photo-product at 400-550 nm indicated that the color change of the Perlodel® 2.5 mg tablet was caused by photochemical degradation of bromocriptine mesylate. Thus, this analysis of the photochemical changes in drugs stored under different light sources demonstrated the potency of LED lights. Through the objective evaluation of the color change, the cause of the color change was determined; this will allow us to develop a strategy that minimizes possible disadvantages to patients, such as a decrease in treatment efficacy owing to decomposition of the main component or adverse caused by decomposed matter.

Clinic-level factors associated with collaboration with community pharmacies in Japan.

The aim of this study was to clarify the clinic-level factors related to experiences of and attitudes toward collaboration with community pharmacies. We conducted a postal questionnaire survey of all clinics in Gifu, Japan, assessing the experiences and attitudes of representative clinical staff regarding the following activities in collaboration with community pharmacists: regional care meetings/service adjustment meetings, case study conferences, joint workshops/continuing education conferences, community services, information sharing through medical cooperation networks, and accompanying community pharmacists during home care. The factors significantly related to experiences of joint workshops/continuing education conferences included home care visits (odds ratio [OR] 2.39) and a 100 % out-of-hospital prescription ratio (OR 4.80). In contrast, only home care visits were significantly associated with consideration of information sharing through medical cooperation networks and accompanying community pharmacists during home care (OR 2.06 and 11.91, respectively). Finally, the factors significantly associated with considering implementing case study conferences and joint workshops/continuing education conferences included home care visits (OR 4.64 and 2.98, respectively) and a 100% out-of-hospital prescription ratio (OR 4.64 and 6.38). Overall, having more opportunities to communicate with community pharmacists and other healthcare professionals appeared to facilitate clinics' consideration of collaboration with community pharmacies, along with actual experiences.

Bone morphogenetic protein signaling mediated by ALK-2 and DLX2 regulates apoptosis in glioma-initiating cells.

Bone morphogenetic protein (BMP) signaling exerts antitumor activities in glioblastoma; however, its precise mechanisms remain to be elucidated. Here, we demonstrated that the BMP type I receptor ALK-2 (encoded by the ACVR1 gene) has crucial roles in apoptosis induction of patient-derived glioma-initiating cells (GICs), TGS-01 and TGS-04. We also characterized a BMP target gene, Distal-less homeobox 2 (DLX2), and found that DLX2 promoted apoptosis and neural differentiation of GICs. The tumor-suppressive effects of ALK-2 and DLX2 were further confirmed in a mouse orthotopic transplantation model. Interestingly, valproic acid (VPA), an anti-epileptic compound, induced BMP2, BMP4, ACVR1 and DLX2 mRNA expression with a concomitant increase in phosphorylation of Smad1/5. Consistently, we showed that treatment with VPA induced apoptosis of GICs, whereas silencing of ALK-2 or DLX2 expression partially suppressed it. Our study thus reveals BMP-mediated inhibitory mechanisms for glioblastoma, which explains, at least in part, the therapeutic effects of VPA.

Intratumoral tertiary lymphoid organ is a favourable prognosticator in patients with pancreatic cancer.

BACKGROUND: Host immunity has critical roles in tumour surveillance. Tertiary lymphoid organs (TLOs) are induced in various inflamed tissues. The aim of this study was to investigate the clinicopathological and pathobiological characteristics of tumour microenvironment in pancreatic ductal carcinoma (PDC) with TLOs. METHODS: We examined 534 PDCs to investigate the clinicopathological impact of TLOs and their association with tumour-infiltrating immune cells, the cytokine milieu, and tissue characteristics. RESULTS: There were two different localisations of PDC-associated TLOs, intratumoral and peritumoral. A better outcome was observed in patients with intratumoral TLOs, and this was independent of other survival factors. The PDC tissues with intratumoral TLOs showed significantly higher infiltration of T and B cells and lower infiltration of immunosuppressive cells, as well as significantly higher expression of Th1- and Th17-related genes. Tertiary lymphoid organs developed with an association with arterioles, venules, and nerves. These structures were reduced in an association with cancer invasion in PDC tissues, except for those with intratumoral TLOs. The PDC tissues with intratumoral TLOs had capillaries consisting of mature endothelial cells covered by pericytes. CONCLUSIONS: Our results suggest that the presence of intratumoral TLOs represents a microenvironment that has an active immune reaction, and shows a relatively intact vascular network retained.

Impact of glucose fluctuation and monocyte subsets on coronary plaque rupture.

BACKGROUND AND AIMS: It remains unclear whether glycemic fluctuation can affect plaque rupture in acute myocardial infarction (AMI). Here we investigate the impact of glucose fluctuation on plaque rupture, as observed by optical coherence tomography (OCT), and monocyte subsets in patients with AMI. METHODS AND RESULTS: We studied 37 consecutive patients with AMI. All patients underwent OCT examination, which revealed 24 patients with plaque rupture and 13 patients without plaque rupture at the culprit site. Peripheral blood sampling was performed on admission. Three monocyte subsets (CD14(+)CD16(-), CD14(bright)CD16(+), and CD14(dim)CD16(+)) were assessed by flow cytometry. Glycemic variability, expressed as the mean amplitude of glycemic excursion (MAGE), was determined by a continuous glucose monitoring system 7 days after the onset of AMI. MAGE was significantly higher in the rupture patients than in the non-rupture patients (P=0.036). Levels of CD14(bright)CD16(+) monocytes from the rupture patients were significantly higher than those from the non-rupture patients (P=0.042). Of interest, levels of CD14(bright)CD16(+) monocytes correlated positively and significantly with MAGE (r=0.39, P=0.02). CONCLUSION: Dynamic glucose fluctuation may be associated with coronary plaque rupture, possibly through the preferential increase in CD14(bright)CD16(+) monocyte levels.

The pleiotrophin-ALK axis is required for tumorigenicity of glioblastoma stem cells.

Increasing evidence suggests that brain tumors arise from the transformation of neural stem/precursor/progenitor cells. Much current research on human brain tumors is focused on the stem-like properties of glioblastoma. Here we show that anaplastic lymphoma kinase (ALK) and its ligand pleiotrophin are required for the self-renewal and tumorigenicity of glioblastoma stem cells (GSCs). Furthermore, we demonstrate that pleiotrophin is transactivated directly by SOX2, a transcription factor essential for the maintenance of both neural stem cells and GSCs. We speculate that the pleiotrophin-ALK axis may be a promising target for the therapy of glioblastoma.

Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer.

BACKGROUND: The host immune reaction is represented by immune/inflammatory cell infiltrates. Here we systematically analysed tumour-infiltrating immune/inflammatory cells in pancreatic ductal carcinoma (PDC) and evaluated their clinicopathological impact. METHODS: Using immunohistochemistry, we examined tumour-infiltrating CD68(+) pan-macrophages, HLA-DR(+)CD68(+) M1 macrophages (M1), CD163(+) or CD204(+) M2 macrophages (M2), CD66b(+) neutrophils (Neu), CD4(+) T cells (CD4(+)T), CD8(+) T cells (CD8(+)T), and FOXP3(+)CD4(+) regulatory T cells (Treg) in 212 cases of PDC, and conducted correlation and survival analyses using the Kaplan-Meier method and Cox proportional hazards model. RESULTS: Higher levels of tumour-infiltrating pan-macrophages, M2, Neu, or the ratio of Tregs to CD4(+)T (%Treg) were significantly associated with shorter survival, whereas higher levels of tumour-infiltrating CD4(+)T, CD8(+)T, or the ratio of M1 to pan-macrophages (%M1) were significantly associated with longer survival. Survival analysis of pairs of these variables revealed that some of the resulting patient groups had exclusively longer survival. We then connected the apparently related factors, and two significant variables emerged: tumour-infiltrating CD4(+)T(high)/CD8(+)T(high)/%Treg(low) and tumour-infiltrating %M1(high)/M2(low). Multivariate survival analysis revealed that these variables were significantly correlated with longer survival and had a higher hazard ratio. CONCLUSION: Tumour-infiltrating CD4(+)T(high)/CD8(+)T(high)/%Treg(low) and %M1(high)/M2(low) are independent prognosticators useful for evaluating the immune microenvironment of PDC.

The critical role of cyclin D2 in cell cycle progression and tumorigenicity of glioblastoma stem cells.

Cancer stem cells are believed to be responsible for tumor initiation and development. Much current research on human brain tumors is focused on the stem-like properties of glioblastoma stem cells (GSCs). However, little is known about the molecular mechanisms of cell cycle regulation that discriminate between GSCs and differentiated glioblastoma cells. Here we show that cyclin D2 is the cyclin that is predominantly expressed in GSCs and suppression of its expression by RNA interference causes G1 arrest in vitro and growth retardation of GSCs xenografted into immunocompromised mice in vivo. We also demonstrate that the expression of cyclin D2 is suppressed upon serum-induced differentiation similar to what was observed for the cancer stem cell marker CD133. Taken together, our results demonstrate that cyclin D2 has a critical role in cell cycle progression and the tumorigenicity of GSCs.

Tumour necrosis is a postoperative prognostic marker for pancreatic cancer patients with a high interobserver reproducibility in histological evaluation.

BACKGROUND: Tumour necrosis reflects the presence of hypoxia, which can be indicative of an aggressive tumour phenotype. The aim of this study was to investigate whether histological necrosis is a useful predictor of outcome in patients with pancreatic ductal carcinoma (PDC). METHODS: We reviewed histopathological findings in 348 cases of PDC in comparison with clinicopathological information. We counted small necrotic foci (micronecrosis) as necrosis, in addition to massive necrosis that had been only defined as necrosis in previous studies. The reproducibility of identifying histological parameters was tested by asking five independent observers to blindly review 51 examples of PDC. RESULTS: Both micronecrosis and massive necrosis corresponded to hypoxic foci expressing carbonic anhydrase IX detected by immunohistochemistry. Multivariate survival analysis showed that histological necrosis was an independent predictor of poor outcome in terms of both disease-free survival (DFS) and disease-specific survival (DSS) of PDC patients. In addition, metastatic status, and lymphatic, venous, and intrapancreatic neural invasion were independent prognostic factors for shorter DFS and metastatic status, margin status, lymphatic invasion, and intrapancreatic neural invasion were independent prognostic factors for DSS. The interobserver reproducibility of necrosis identification among the five independent observers was 'almost perfect' (κ-value of 0.87). CONCLUSION: Histological necrosis is a simple, accurate, and reproducible predictor of postoperative outcome in PDC patients.

Breed differentiation among Japanese native chickens by specific skull features determined by direct measurements and computer vision techniques.

1. Inter-breed morphological comparisons were made among 11 breeds of Japanese native chickens (Gifujidori, Hinaidori, Shokoku, Totenko, Tomaru, Satsumadori, Shamo, Koshamo, Koeyoshi, Chabo and Nagoya), White Leghorn, broiler chickens (Chunky) and red junglefowl collected in the Philippines, based on results of direct measurements and analysis by computer vision techniques of the skull. 2. Analysis of direct measurements identified two groups of chicken: a small type that included the Chabo, Koshamo, red junglefowl, Gifujidori and Shokoku and a large type that included the remaining breeds studied. These groupings were made based on size determined both in the first (PC1) and second principal component (PC2). The greatest length of the cranium and condylobasal length greatly contributed to the morphological differences between these two groups. 3. Analysis by computer vision techniques, however, identified three groups: the Bantam group (which includes red junglefowl), Shokoku group and Shamo group. White Leghorn clustered within the Shokoku group while the broiler chicken belonged to the Shamo group. The region around the junction of the neural cranium and the visceral cranium contributed greatly to the morphological differences among breeds, both in the PC1 and PC2.

Analysis of mtDNA sequences shows Japanese native chickens have multiple origins.

In this study, we analysed the mitochondrial DNA D-loop region of Japanese native chickens to clarify their phylogenetic relationships, possible maternal origin and routes of introduction into Japan. Seven haplogroups (Types A-G) were identified. Types A-C were observed in Jidori, Shokoku and related breeds. However, Type C was absent in Shokoku, which was introduced from China, while most Indonesian native chickens were included in the Type C haplogroup. Types D-G were observed in Shamo and related breeds. Type E had a close genetic relationship with Chinese native chickens. Our results indicate that some breeds were not introduced into Japan as suggested in conventional literature, based on low nucleotide diversity of certain chicken breeds. Sequences originating from China and Korea could be clearly distinguished from those originating from Southeast Asia. In each group, domestic chickens were divided into the Jidori-Shokoku and Shamo groups. These results indicate that Chinese and Korean chickens were derived from Southeast Asia. Following the domestication of red junglefowl, a non-game type chicken was developed, and it spread to China. A game type chicken was developed in each area. Both non-game and game chickens formed the foundation of Japanese native chickens.

Involvement of c-Src in carcinoma cell motility and metastasis.

Carcinoma cells exhibit dysfunction / dysregulation of cell adhesion systems that correlates with their abilities to migrate, invade, and metastasize. Here we show that the tyrosine kinase c-Src is required for motility and metastasis of two carcinoma cell lines. Adherent KYN-2 cells having a high level of c-Src kinase activity become scattered, extend lamellipodia, and exhibit high motility. Expression of a dominant-negative mutant form of c-Src caused formation of stress fibers and focal adhesions, and markedly reduced motility. HCT15 cells extended lamellipodia and became scattered in response to lysophosphatidic acid stimulation in parallel with transient activation of c-Src, which was inhibited by expression of a dominant-negative mutant form of c-Src or treatment with a specific Src kinase inhibitor. Furthermore, implantation of dominant-negative c-Src transfectants into the peritoneal cavity of SCID mice resulted in reduced peritoneal dissemination compared with control transfectants. These findings indicate that c-Src activation is critically involved in carcinoma cell migration and metastasis.

PTEN is a target of chromosome 10q loss in anaplastic oligodendrogliomas and PTEN alterations are associated with poor prognosis.

Allelic loss of 10q is a common genetic event in malignant gliomas, with three 10q tumor suppressor genes, ERCC6, PTEN, and DMBT1, putatively implicated in the most common type of malignant glioma, glioblastoma. Anaplastic oligodendroglioma, another type of malignant glioma, provides a unique opportunity to study the relevance of particular genetic alterations to chemosensitivity and survival. We therefore analyzed these three genes in 72 anaplastic oligodendrogliomas. Deletion mapping demonstrated 10q loss in 14 of 67 informative cases, with the PTEN and DMBT1 regions involved in all deletions but with the ERCC6 locus spared in two cases. Seven tumors had PTEN gene alterations; two had homozygous DMBT1 deletions, but at least one reflected unmasking of a germline DMBT1 deletion. No mutations were found in ERCC6 exon 2. Chemotherapeutic response occurred in two of the seven tumors with PTEN alterations, but with unexpected short survival times. PTEN gene alterations were not associated with poor therapeutic response in multivariate analysis, but were independently predictive of poor prognosis even after multivariate adjustment for both 10q and 1p loss. In anaplastic oligodendroglioma, therefore, PTEN is a target of 10q loss, and PTEN alterations are associated with poor prognosis, even in chemosensitive cases.

Molecular subtypes of anaplastic oligodendroglioma: implications for patient management at diagnosis.

PURPOSE: In a prior study of anaplastic oligodendrogliomas treated with chemotherapy at diagnosis or at recurrence after radiotherapy, allelic loss of chromosome 1p correlated with better chemotherapeutic response and overall survival. However, in this group of patients in whom therapeutic management was not uniform, loss of 1p did not identify all chemosensitive tumors, nor did all patients whose tumors harbor a 1p loss have long survival. EXPERIMENTAL DESIGN: To clarify the clinical relevance of molecular genetic testing at the time of diagnosis for patients with anaplastic oligodendrogliomas, we studied a larger, more homogeneous group of 50 patients with histologically defined anaplastic oligodendrogliomas treated with a chemotherapeutic regimen as the principal initial therapy. RESULTS: We demonstrate that these tumors can be divided genetically into four therapeutically and prognostically relevant subgroups. Patients whose tumors have combined but isolated losses of 1p and 19q have marked and durable responses to chemotherapy associated with long survival, with or without postoperative radiation therapy. Other tumors with chromosome 1p alterations also respond to chemotherapy, but with shorter duration of response and patient survival. Tumors lacking 1p loss can also be divided into two subgroups: those with TP53 mutations, which may also respond to chemotherapy but recur quickly, and those without TP53 mutations, which are poorly responsive, aggressive tumors that are clinically and genotypically similar to glioblastomas. CONCLUSIONS: These data raise the possibility, for the first time, that therapeutic decisions at the time of diagnosis might be tailored to particular genetic subtypes of anaplastic oligodendroglioma.

Molecular genetics of radiographically defined de novo glioblastoma multiforme.

Glioblastoma multiforme (GBM) represents the final endpoint of anaplastic progression in astrocytomas. GBM which arise without clinical evidence of a prior low-grade astrocytoma (LGA) have been designated de novo GBM, and are thought to develop rapidly from initial tumour formation. However, a purely clinical definition of de novo GBM does not exclude a long-standing, asymptomatic low-grade tumour. This study therefore sought to determine the genetic features of a unique group of cases in which GBMs were documented to have arisen radiographically in defined period of time (radiographically defined de novo GBM). Clinical and genetic features were examined in a group of 11 patients with a histological diagnosis of high-grade astrocytoma at first biopsy and radiographically defined de novo GBM. The mean age of the patients at tumour diagnosis was 62 years (range 32-87). Six of 11 tumours arose in the temporal lobes. Eight of 11 tumours had epidermal growth factor receptor (EGFR) overexpression, and EGFR gene amplification was found in five of the six analysed cases. Overexpression of p53 was observed in only one tumour, and a TP53 mutation was present in this case. p16 immunostaining was undetectable in 10 cases, and homozygous deletion of CDKN2A was observed in four of the six studied tumours. pRb expression was lost in four tumours. Mutations in the PTEN gene were detected in two of six cases. The results in this unique group of cases confirms the prior hypothesis that the profile of genetic alterations in de novo GBM is distinct from that of GBM arising from a known LGA, and that these specific genetic pathways promote the rapid development of GBM.

Allelic loss of chromosome 1p and radiotherapy plus chemotherapy in patients with oligodendrogliomas.

INTRODUCTION: Allelic loss of the short arm of chromosome 1 predicts radiographic response to chemotherapy and long overall survival times in patients with anaplastic oligodendrogliomas. Using a database of patients with oligodendrogliomas in whom chromosome 1p status was known, we explored whether allelic loss of 1p also predicted longer duration of tumor control when radiotherapy was part of the initial treatment of these patients. MATERIALS AND METHODS: We measured progression-free survival following radiotherapy in a cohort of patients with World Health Organization (WHO) Grade II and WHO Grade III oligodendrogliomas. The effects on progression-free survival of patient age, Karnofsky performance score (KPS), tumor grade when irradiated and chromosome 1p status were examined by univariate and multivariate statistical analyses. For the subset of patients with newly diagnosed anaplastic oligodendrogliomas, relationships between use of chemotherapy, chromosome 1p status and progression-free survival were also examined. RESULTS: Fifty-five patients (29 male, 26 female; ages 18-75 years; median, 44 years; KPS 50-90, median 80) were irradiated for either a WHO Grade II (n = 19) or Grade III (n = 36) oligodendroglioma. Twenty-eight patients had chemotherapy immediately prior to radiotherapy, and 27 had chemotherapy at progression following radiotherapy. The median radiation dose was 54 Gy in 30 fractions. Loss of heterozygosity (LOH) at chromosome 1p was evident in 36 tumors and absent in 19. Overall median progression-free survival after radiotherapy was 40.4 months. Median progression-free survival was 55.0 months for patients whose tumors harbored 1p loss vs. 6.2 months for those patients whose tumors retained both copies of chromosome 1p (p < 0.001). On both univariate and multivariate analyses, chromosome lp loss was the principal independent predictor of longer progression-free survival for patients with Grade II and III oligodendrogliomas. For Grade III oligodendrogliomas, chemotherapy as an adjunct to radiotherapy prolonged tumor control for those patients whose tumors harbored allelic loss of chromosome 1p (p = 0.004). CONCLUSION: These data suggest allelic loss of chromosome 1p in patients with oligodendroglial neoplasms predicts longer progression-free survival among patients receiving radiotherapy +/- chemotherapy as part of their initial treatment. Chromosome 1p loss may be an important stratification variable in future therapeutic trials of oligodendroglioma.

Involvement of eosinophils in the early-phase allergic reaction in a guinea pig rhinitis model.

BACKGROUND: Eosinophils are found in the nasal lavage fluid (NLF) and nasal biopsies of patients with allergic rhinitis after a nasal antigen challenge, and associated not only with a late-phase allergic reaction (LPR) but also an early phase allergic reaction (EPR). Numerous studies have been carried out to clarify the participation of eosinophils in LPR or airway hyperresponsiveness. However, there has been no published report describing in detail the role of eosinophils during EPR. To better understand the involvement of eosinophils in EPR, we studied the effects of repeated antigen challenges on nasal airway responsiveness and eosinophilic inflammation in EPR using a guinea pig rhinitis model. METHODS: Nasal airway responsiveness was measured as the nasal airway resistance (NAR) after nasal antigen provocation. Eosinophilic inflammation during EPR was assessed by nasal lavage and histopathological examination using two groups of animals: those in group 1 were subjected to a sensitization pretreatment only, and those in group 2 were subjected to a pretreatment of sensitization followed by repeated nasal challenges. RESULTS: Repeated antigen challenges induced nasal hyperresponsiveness as indicated by a decrease in the antigen provocation dose and a significant increase in NAR. Furthermore, significant increases in eosinophil counts, eosinophil peroxidase (EPO) activity and protein content in NLF during EPR were observed following antigen provocation in group 2. There were significant correlations between the levels of these parameters, and albumin was the most prevalent of the proteins in NLF. Histopathological examination showed that the degree of eosinophil infiltration into the lamina propria of the nasal mucosa of the animals in group 2 was significantly and apparently higher than in group 1. Particularly, epithelial disruption and mucosal edema were significantly elevated after antigen provocation in group 2. CONCLUSIONS: These results suggest that chronic eosinophil accumulation is induced by repeated antigen challenges in the nasal tissue, and that once antigen provocation occurs, eosinophils in the tissue are activated and responsible for the amplification of EPR such as vascular permeability and mucosal edema.

Primary lymphoma of peripheral nerve: report of four cases.

Lymphoma presenting as a solitary tumor of peripheral nerve is exceedingly rare, with only six previously reported cases. The authors describe an additional four cases of primary lymphoma of peripheral nerve involving the sciatic nerve (two cases), the radial nerve, and the sympathetic chain and spinal nerve. The patients were two men and two women with an average age of 55.5 years. All tumors were high-grade B-cell lymphomas. Two patients experienced relapse of disease with involvement of other nervous system sites and died of lymphoma. One patient is alive with stable local disease at 57 months. The fourth patient is alive with no evidence of disease at 54 months. Expression of neural cell adhesion molecule (CD56) has been reported to correlate with an increased incidence of central nervous system involvement in peripheral T-cell lymphoma; all their cases were CD56 negative. Recent reports indicate a high proportion of primary brain lymphomas show loss of CDKN2A/p16 gene expression. Therefore, CDKN2A/p16 was evaluated in their patients both by polymerase chain reaction and by immunohistochemistry for the p16 protein. The authors found homozygous deletion of the CDKN2A/p16 gene in one of three patients studied, confirmed immunohistochemically by absent staining for p16. The fourth patient showed absent staining for p16, suggesting inactivation of the gene in this case as well. The two patients with p16 loss both died of lymphoma, whereas the two patients with normal p16 expression are alive. Primary lymphoma of peripheral nerve is a rare neoplasm, usually of large B-cell type, has a variable prognosis, and appears to have less consistent loss of p16 expression than primary central nervous system lymphoma.