Changes of HER2 low expression status in primary and recurrent/metastatic breast cancer / 中华病理学杂志

Objective: To investigate the evolution and clinical significance of HER2 low expression status in HER2 negative patients in primary and recurrent/metastatic breast cancers. Methods: The data and archived sections of 259 breast cancer patients with recurrence/metastasis and HER2-negative primary foci were collected from January 2015 to January 2022 at the Fourth Hospital of Hebei Medical University, and the HER2 status of primary and recurrence/metastasis foci was determined by immunohistochemistry (IHC), among which IHC 2+patients were subject to fluorescence in situ hybridization (FISH). The HER2 status was classified as HER2-0 group; patients with IHC 1+, IHC 2+and no FISH amplification were classified as HER2 low expression group; and patients with IHC 3+, IHC 2+and FISH amplified were classified as HER2-positive group. The changes of HER2 status in patients with HER2 low expression in primary versus recurrent/metastatic breast cancer foci were compared, and their clinicopathologic characteristics and prognosis were analyzed. Results: The overall concordance rate between primary and recurrent/metastatic HER2 status in breast cancer was 60.6% (157/259, κ=0.178). A total of 102 patients (102/259, 39.4%) had inconsistent primary and recurrent/metastatic HER2 status; 37 patients (37/259, 14.3%) had HER2-0 at the primary foci and HER2-low expression at the recurrent/metastatic; and 56 patients (56/259, 21.6%) had HER2-low expression in the primary foci and HER2-0 in the recurrent/metastatic. The recurrent/metastatic foci became low-expressing compared with the recurrent/metastatic foci which remained HER2-0 patients, with longer overall survival time, higher ER and PR positivity, lower Ki-67 positivity index, and lower tumor histological grade; all with statistically significant differences (all P<0.05). In the primary HER2-low group, patients with recurrent/metastatic foci became HER2-0 while those with recurrent/metastatic foci remained low expression; there were no statistically significant differences in clinicopathological features and overall survival time (all P>0.05). Conclusions: Unstable HER2 status in patients with HER2-0 and low expression in primary versus recurrent/metastatic breast cancer foci, and HER2-0 in the primary foci but low HER2 expression status in recurrence/metastasis is associated with favourable prognosis, and testing HER2 status in recurrence/metastasis can provide more treatment options for such patients.

Association between nuclear factor kappa-light-chain-enhancer of activated B cells genetic polymorphisms and HCV susceptibility among the Chinese population under high-risk / 中华流行病学杂志

Objective: To explore the association between nuclear factor kappa-light-chain-enhancer of activated genetic polymorphisms in B cells (NF-κB) and the HCV susceptibility, among the Chinese population. Methods: A total of 1 679 participants were enrolled; including 503 drug users and 1 176 other participants at risk under the exposure for blood. By using the logistic regression analysis, related risk factors for HCV infection among subjects were analyzed. Two NF-κB pathway variants, NF-κB1 rs72696119 and REL rs13031237 were then genotyped by TaqMan assay method. Logistic regression analysis was performed to analyze the association between gene polymorphisms and the susceptibility on HCV. Results: Among the drug users, women (OR=0.408, 95%CI: 0.308-0.767) appeared to be associated with the decreased risk for HCV infection, while factors as drug injection (OR=8.817, 95%CI: 5.577-13.937) and the duration of drug-intake >5.5 years (OR=2.891, 95%CI: 1.824-4.583) were associated with the increased risk for HCV infection. Among the participants who had been exposed to blood, women (OR=3.431, 95%CI: 2.360-4.988) were associated with the increased risk for HCV infection, while the levels of education beyond elementary school (OR=0.613, 95%CI: 0.429-0.876) were associated with the decreased risk for HCV infection. Compared to the reference NF-κB1 rs72696119 CC genotype, the carriage of GG genotype was associated with an increased risk of susceptibility on HCV (OR=1.412, 95%CI: 1.035-1.927) among the total study population. Results from the interaction analysis showed that there was no interactive effects appeared between rs72696119 and route of infection, or between rs72696119 and gender among the total population under study (all P>0.05). Conclusion: NF-κB1 polymorphism rs72696119 and related factors seemed associated with the susceptibility to HCV infection among high-risk Chinese populations.