Immunohistochemical detection of intranuclear p53 gene product may indicate mutation of the p53 suppressor gene on chromosome 17p. We used six commercially available antibodies for p53 immunohistochemistry on 19 archival colorectal neoplasms and compared the results with the mutation status of the p53 gene and 17p allelic deletion status. By Friedman's ranking analysis, use of mouse monoclonal antibody DO7 with Target Unmasking Fluid (TUF) for antigen retrieval was the most sensitive and specific procedure (P < 0.0001). Six of 7 cases with high expression (p53 Labeling Index > 30 per cent using a CAS 200 image analyser) had p53 mutation. Of seven tumours without expression (LI < 1 per cent), six had no mutation and one had a truncating mutation which prohibited nuclear localization of gene product. The low expression group (1 per cent < LI < 30 per cent, n = 5) consisted of three tumours without and two tumours with mutation. The sensitivity of high expression with the DO7-TUF method for p53 gene mutation was 67 per cent with specificity of 90 per cent, predictive value of a positive of 86 per cent, predictive value of a negative of 75 per cent, and efficiency of 79 per cent. This study suggests that immunohistochemistry is valuable for assessing p53 gene mutations in colorectal neoplasms, but further study is needed to elucidate the precise link between immunohistochemistry and molecular genetic alterations.

Background The COVID-19 pandemic (officially declared on the 11th of March, 2020), and the resulting measures, are impacting daily life and medical management of breast cancer patients and survivors. We evaluated to what extent these changes have affected quality of life, physical and psychosocial wellbeing of patients (being) treated for breast cancer. Methods This study was conducted within a prospective, multicentre cohort of breast cancer patients and survivors (UMBRELLA). Shortly after the implementation of COVID-19 measures, an extra survey was sent to 1,595 participants, including validated EORTC QLQ-C30/BR23 and HADS questionnaires. Patient-reported outcomes (PROs) were compared to the most recent PROs collected within UMBRELLA pre-COVID-19. The impact of COVID-19 on PROs was assessed using mixed model analysis, adjusting for potential confounders. Results 1,051 patients and survivors (65.9%) completed the survey; 31.1% (n = 327) reported a higher threshold to contact their general practitioner amid the COVID-19 pandemic. A statistically significant deterioration in emotional functioning was observed (82.6 [SD = 18.7] to 77.9 [SD = 17.3], p &lt; .001), and 505 (48.0%, 95%CI = 45.0 to 51.1%) reported moderate to severe loneliness. Small improvements were observed in QoL, physical-, social- and role functioning. In the subgroup of 51 patients under active treatment, social functioning strongly deteriorated (77.3 [95%CI = 69.4 to 85.2] to 61.3 [95%CI = 52.6 to 70.1], p = .002). Conclusion During the COVID-19 pandemic, breast cancer patients and survivors were less likely to contact physicians and experienced a deterioration in their emotional functioning. Patients undergoing active treatment reported a substantial drop in social functioning. One in two reported loneliness that was moderate or severe. Online interventions supporting mental health and social interaction are needed during times of social distancing and lockdowns.

Humoral immune responses are tailored to the invading pathogen through regulation of key transcription factors and their networks. This is critical to establishing effective antibody-mediated responses, yet it is unknown how B cells integrate pathogen-induced signals to drive or suppress transcriptional programs specialized for each class of pathogen. Here, we detail the key role of the transcription factor c-Myb in regulating the T-bet-mediated anti-viral program. Deletion of c-Myb in mature B cells significantly increased serum IgG2c and CXCR3 expression by upregulating T-bet, normally suppressed during Th2-cell-mediated responses. Enhanced expression of T-bet resulted in aberrant plasma cell differentiation within the germinal center, mediated by CXCR3 expression. These findings identify a dual role for c-Myb in limiting inappropriate effector responses while coordinating plasma cell differentiation with germinal center egress. Identifying such intrinsic regulators of specialized antibody responses can assist in vaccine design and therapeutic intervention in B-cell-mediated immune disorders.

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Summary~Mutation of the p53 gene is reported to be of prognostic importance in colorectal carcinomas. Immunohistochemical staining of the accumulated p53 gene product may be a simple alternative for p53 mutation analysis. Previous studies addressing the prognostic importance of p53 expression. however, yielded contradictory results. Therefore, we evaluated the importance of p53 expression as a marker for long-term prognosis in a well-characterised study population of 109 colorectal carcinomas. After antigen retrieval with target unmasking fluid (TUF). immunostaining of p53 was performed with both monoclonal antibody D07 and polyclonal antibody CMI. Objective quantification of the p53 signal was assessed by a computerised image analyser. p53 expression was higher in non-mucinous tumours than in mucinous tumours (p53 labelling index = 30% and 17% respectively, P = 0.05), and in metastatic tumours compared with non-metastatic tumours (p53 labelling index = 37% and 22% respectively, P = 0.05 Lane, 1992;Levine, 1992aLevine, , 1992bOren, 1992;Vogelstein and Kinzler, 1992). It is located on the short arm of chromosome 17 in the region 17pl3 and encodes a 53 kDa nuclear phosphoprotein that serves as a transcription factor El-Deiry et al., 1993). The p53 protein indirectly regulates cell growth and inhibits cells with mutagenic damage from entering the S-phase by arresting the cell cycle in GI, during which DNA repair can proceed.In colorectal cancer, p53 mutations are frequently accompanied by allelic loss of 17p (Baker et al., 1989;Rodrigues et al., 1990). Both p53 mutations and allelic deletion of 17p occur late in tumour progression (Baker et al., 1990) and are reported to have prognostic value after surgery (Kern et al., 1989;Laurent-Puig et al., 1992;Offerhaus et al., 1992; Hamelin et al., 1994 In the p53-tested cohort of 109 patients, there were 56 men and 53 women; the median age was 66 years (mean age 65 years, s.d. = 10 years, range 25-96 years). Twenty-two tumours were located in the caecum or ascending colon, eight in the transverse colon or splenic flexure, 46 in the descending colon or sigmoid and 33 tumours in the rectum. Tumours

Aim-To evaluate similarities and diVerences between gastric stump cancer and conventional carcinoma in the nonoperated stomach. Methods-26 stump carcinomas were compared with 24 conventional stomach cancers. Stage, histological type, and demographics were comparable in the two groups. Expression of p53 and p21-Waf1/ Cip1 was evaluated by immunohistochemical staining. Helicobacter pylori infection was evaluated by examining haematoxylin-eosin stained slides and immunohistochemistry.Epstein-Barr virus infection was evaluated by RNA in situ hybridisation. Results-Expression of p53 and p21-Waf1/ Cip1 was similar in both groups and positive in more than half of the patients. H pylori infection was observed in six stump carcinomas and 17 conventional carcinomas in the intact stomach (p < 0.01). RNA in situ hybridisation (EBER1-ISH) for Epstein-Barr virus was positive in nine stump carcinomas and two carcinomas in the non-operated stomach (p < 0.05). Conclusions-There appear to be aetiological diVerences between stump carcinoma and cancer in the intact stomach. Further study of these diVerences may improve our understanding of gastric carcinogenesis in general. (J Clin Pathol 1998;51:662-666)

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Summary Inactivation of the p53 tumour-suppressor gene is common in a wide variety of human neoplasms. In