Prognostic significance of lymphatic vessel invasion diagnosed by D2-40 in Chinese invasive breast cancers.

Lymphatic vessel invasion (LVI) is promising in determining prognosis and treatment strategies, but the application of LVI as a histopathological criterion in breast cancer patients especially those of different subgroups is controversial. This research aims to evaluate the prognostic value of LVI assessed by D2-40 not only in patients with early invasive breast cancer but also in lymph node-negative, lymph node-positive, luminal A-like, luminal B-like, HER2-enriched, and triple-negative subgroups.The study cohort included 255 patients with a median follow-up of 101 months. Immunohistochemical staining for D2-40 was performed to identify LVI.LVI was present in 64 (25.1%), 15 (12.1%), 49 (37.4%), 19 (20.9%), 23 (27.7%), 13 (31.7%), and 9 (22.5%), respectively, in the whole cohort, lymph node-negative, lymph node-positive, luminal A-like, luminal B-like, HER2-enriched, and triple-negative patients. LVI was associated with large tumor size (P = .04), high histological grade (P = .004), involved lymph node (P < .001), and high expression of Ki-67 (P = .003). No significant difference was found among patients with different subtypes and LVI status. The presence of LVI was significantly associated with adverse disease-free survival in the whole cohort (P < .001), lymph node-negative (P < .001), lymph node-positive (P < .001), luminal A-like (P < .001), and luminal B-like patients (P < .001) in both of the univariate and multivariate survival analysis.This study indicated that the presence of LVI stained by D2-40 provided independent prognostic information not only in the whole cohort but also in the subgroup of patients with lymph node-negative, lymph node-positive, luminal A-like, and luminal B-like diseases, which may make a case for routine clinical assessment of LVI using D2-40.

Primary or metastatic hepatic carcinoma? A breast cancer patient after adjuvant chemotherapy and radiotherapy postoperatively with intrahepatic cholangiocarcinoma and review of the literature.

BACKGROUND: The liver is a common site of metastases, followed by the bone and lung in breast cancer. The symptoms of hepatic metastases are similar to intrahepatic cholangiocarcinoma (ICC). ICC is rare, with an overall incidence rate of 0.95 cases per 100,000 adults. The incidence of ICC for patients with breast cancer is very uncommon. Breast cancer patient with ICC is easily misdiagnosed as hepatic metastases. CASE PRESENTATION: We report a breast cancer patient postoperatively who was hospitalized because of having continuous irregular fever for 1 month. Antibiotics were given for 1 week without any significant effect. Her admission bloods revealed elevated levels of carcino-embryonic antigen. Magnetic resonance imaging diagnosis showed multiple liver metastases. We believed that the woman had hepatic metastases until biopsy guided by computed tomography. The liver biopsy pathology analysis considered the possibility of primary intrahepatic cholangiocarcinoma. CONCLUSIONS: Breast cancer patient with space-occupying lesions in the liver is easily considered to be progressed hepatic metastases. Image-guided biopsy is the best diagnostic method for breast cancer with liver mass to avoid misdiagnosis and classify the molecular subtypes to make appropriate treatment.

UNC-64 and RIC-4, the plasma membrane-associated SNAREs syntaxin and SNAP-25, regulate fat storage in nematode Caenorhabditis elegans.

OBJECTIVE: To investigate whether genes required for synaptogenesis and synaptic function are also involved in fat storage control in Caenorhabditis elegans. METHODS: Fat storage was examined in mutants of genes affecting the synaptogenesis and synaptic function. In addition, the genetic interactions of SNAREs syntaxin/unc-64 and SNAP-25/ric-4 with daf-2, daf-7, nhr-49, sbp-1 and mdt-15 in regulating fat storage were further investigated. The tissue-specific activities of unc-64 and ric-4 were investigated to study the roles of unc-64 and ric-4 in regulating fat storage in the nervous system and/or the intestine. RESULTS: Mutations of genes required for the formation of presynaptic neurotransmission site did not obviously influence fat storage. However, among the genes required for synaptic function, the plasma membrane-associated SNAREs syntaxin/unc-64 and SNAP-25/ric-4 genes were involved in the fat storage control. Fat storage in the intestinal cells was dramatically increased in unc-64 and ric-4 mutants as revealed by Sudan Black and Nile Red strainings, although the fat droplet size was not significantly changed. Moreover, in both the nervous system and the intestine, expression of unc-64 significantly inhibited the increase in fat storage observed in unc-64 mutant. And expression of ric-4 in the nervous system completely restored fat storage in ric-4 mutant. Genetic interaction assay further indicated that both unc-64 and ric-4 regulated fat storage independently of daf-2 [encoding an insulin-like growth factor-I (IGF-I) receptor], daf-7 [encoding a transforming growth factor-beta (TGF-beta) ligand], and nhr-49 (encoding a nuclear hormone receptor). Besides, mutation of daf-16 did not obviously affect the phenotype of increased fat storage in unc-64 or ric-4 mutant. Furthermore, unc-64 and ric-4 regulated fat storage probably through the ARC105/mdt-15- and SREBP/sbp-1-mediated signaling pathways. In addition, fat storage in unc-64; ric-4 was higher than that in either unc-64 or ric-4 single mutant nematodes, suggesting that unc-64 functions in parallel with ric-4 in regulating fat storage. CONCLUSION: The plasma membrane-associated SNAREs syntaxin/unc-64 and SNAP-25/ric-4 function in parallel in regulating fat storage in C. elegans, probably through the ARC105/mdt-15- and SREBP/sbp-1-mediated signaling pathways.

Regulation of aging by unc-13 and sbt-1 in Caenorhabditis elegans is temperature-dependent.

OBJECTIVE: To investigate the role of environmental factor-temperature in the regulation of aging process by unc-13 and sbt-1 in Caenorhabditis elegans. METHODS: The lifespan, the speed of pharynx pumping, and the intestinal autofluorescence of unc-13 and sbt-1 mutants were examined at different temperature conditions. In addition, to exclude the possible influences from other factors in unc-13 and sbt-1 mutants, the dauer formation, the thermotaxis, the brood size and the population percentage of the mutants expressing hsp16.2-gfp were further investigated. RESULTS: Mutations of unc-13 and sbt-1 significantly increased the mean and the maximum lifespans of nematodes cultured at 20 degrees C and 25 degrees C, while no noticeable increase was found at 15 degrees C in either the mean or the maximum lifespan. Investigations on the speed of pharynx pumping and the intestinal autofluorescence suggested that at 20 degrees C and 25 degrees C, mutations of unc-13 and sbt-1 could slow the aging process and delay the accumulation of aging-related cellular damage. Meanwhile, mutations of unc-13 or sbt-1 did not affect the dauer formation or the thermotaxis to different temperatures in nematodes. In contrast, at 20 degrees C and 25 degrees C conditions, mutations of unc-13 and sbt-1 significantly decreased the brood size and the percentage of nematodes expressing hsp16.2-gfp, while no such differences were detected at 15 degrees C. Moreover, the thermotolerance of unc-13 and sbt-1 mutants could be greatly strengthened after the 16-h heat shock at 35 degrees C. CONCLUSION: The regulation of aging by unc-13 and sbt-1 is temperature-dependent. And the alterations in reproduction capability and stress response may be associated with the formation of this temperature-dependent property.