Impact of the updated 2018 ASCO/CAP guidelines on HER2 FISH testing in invasive breast cancer: a retrospective study of HER2 fish results of 2233 cases.

OBJECTIVES: Human epidermal growth factor receptor 2 (HER2, ERBB2) is a valuable prognostic and predictive biomarker in breast cancer. Accurate assessment of HER2 status is essential in selecting the patients with invasive breast cancer who will likely response to HER2-targeted therapies. Some major modifications in the diagnostic recommendation for fluorescence in situ hybridization (FISH) have been made in the updated 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologist (CAP) guideline. According to the revised guideline, concomitant IHC assays are required to arrive at the most accurate HER2 status designation after HER2 FISH equivocal results; however, little is known about its influence on the clinical practice of pathologist. The purpose of this study was to evaluate the impact of the revised 2018 ASCO/CAP guidelines on the HER2 status designation. METHODS: We retrospectively reviewed the HER2 FISH testing results from 2233 cases of invasive breast cancer between January 2014 and December 2017. Concomitant immunohistochemistry (IHC) were performed on the same tissue blocks that were used for the FISH testing. RESULTS: Compared to the 2013 guidelines, the HER2 status in 183 (8.2%) cases were re-defined when reassessed by the 2018 guidelines. Among these 183 cases, 175 equivocal cases according to the 2013 guideline were re-defined as HER2 negative (n = 173) or HER2 positive (n = 2). Eight previously classified as HER2 positive cases were converted to negative in the 2018 scheme, all of which were with HER2 IHC scores of 1+ or 2+. The number of cases in the negative category was 1705 according to the 2018 guidelines as opposed to 1524 by the 2013 guidelines. CONCLUSIONS: The updated 2018 ASCO/CAP guidelines eliminated the FISH equivocal category, which can be attributed to reflex HER2 IHC, and partly ease the dilemma for clinical practice. Reflex IHC for FISH equivocal cases is of prime importance; furthermore, HER2 FISH results were converted from positivity to negativity based on the concomitant IHC results in a small percentage of cases. In all, implementation of the 2018 ASCO/CAP guidelines provides much clearer instructions and recommendations for the HER2 status designation, and thus reduces the risk of misdiagnosis.

Description of a new species of the genus Woznessenskia from Xizang, China (Orthoptera: Gryllacrididae).

The gryllacridid genus Woznessenskia Gorochov, 2002 comprises 13 extant species from Asia, with 8 species reported from China and 5 species reported from Vietnam. A new species from Xizang, China, Woznessenskia lianhua sp. nov., is reported in this paper.

[Dual-color silver-enhanced in-situ hybridization and fluorescence in-situ hybridization for determination of HER2 gene status in gastric carcinoma].

OBJECTIVE: To investigate the advantages and disadvantages of dual-color silver-enhanced in-situ hybridization (DSISH) and fluorescence in-situ hybridization (FISH) for determination of HER2 gene status in gastric carcinoma and to evaluate the feasibility of DSISH. METHODS: Eighty cases of primary gastric or gastroesophageal junction adenocarcinomas diagnosed and treated surgically from January to March, 2009 at the West China Hospital were enrolled in the study. Automated immunohistochemistry (IHC) staining, FISH and automated DSISH were carried out to detect the HER2 status, respectively, and the concordance of the three techniques was then evaluated. RESULTS: DSISH and FISH failed initially, but repeated detection was successful in 5 cases. Gene amplification was detected in 12/13 IHC 3+ cases in DSISH and in 11/13 IHC 3+ cases in FISH. In 6 IHC 2+ cases, the amplification rate was both 1/6; in 18 IHC 1+ cases, the amplification rate was both 2/18. No amplification was observed in 43 IHC 0 cases. Only one of the 80 cases showed discrepancy, and therefore the overall concordance between FISH and DSISH was 98.8% (κ = 0.958, P < 0.01). CONCLUSIONS: DSISH represents a novel approach for the determination of HER2 status in gastric carcinoma, and the overall concordance between DSISH and FISH is excellent. Despite their advantages and disadvantages, DSISH is more feasible and practical for routine application in surgical pathology.

[Clinical characteristics and outcomes of cerebral venous sinus thrombosis during pregnancy and puerperium].

OBJECTIVE: To explore the clinical features and outcomes of patients with cerebral venous sinus thrombosis (CVT) during pregnancy and puerperium. METHODS: A retrospective study was performed in 24 cases of pregnant women with CVT among 15 625 deliveries in Xuanwu Hospital from January 2002 to October 2009, including 7 cases happened during pregnancy and 17 during puerperium. The etiology, clinical presentations, imaging examination results, other relevant examinations, and pregnant outcomes of these patients were analyzed. RESULTS: (1) Incidence and etiology: the incidence of CVT during pregnancy and puerperium was 0.15% (24/15 652) and 29% (7/24) of the patients fell ill during pregnancy and 71% (17/24) during puerperium. Five were complicated with severe preeclampsia, while another 5 complicated with hyperemesis. One woman was complicated with anemia. CVT was identified after spontaneous delivery in 9 cases and 8 after cesarean section. (2) CLINICAL PRESENTATIONS: Among the 24 CVT cases, 22 (92%) suffered from headache, 16 (67%) reported nausea and vomiting, 15(63%) experienced hyperspasmia and 6 (25%) complained of blurred vision. On admission, 8 (33%) patients were unconscious, 3 (13%) with hemiplegia, and 8 (33%) were febrile. (3) Imaging and laboratory examinations: twelve patients underwent digital subtraction arteriography (DSA) and were diagnosed. Fifteen women showed superior sagittal sinus thrombosis in MRI and magnetic resonance intravenous angiograph (MRV). Examination of the fundus found papilledema in 4 cases. Normal cerebral sinus fluid and laboratory routine tests were reported in 13 cases, but 6 cases of hyperlipidemia, 7 cases of abnormal activated partial thromboplastin time (APTT), 5 cases of abnormal international normalized ratio (INR), 3 cases elevated platelet count, 4 cases of positive D-dipolymer, 1 cases of low hemoglobulin level (<10 g/L), 4 cases with abnormal hematocrit, and 10 cases of elevated fibrinogen (>4 g/L) were identified. (4) Management and pregnancy outcomes: among the 7 cases happened during pregnancy, 2 were complicated with severe preeclampsia and delivered through cesarean section immediately and discharged after proper management including depressurization, spasmolysis, dehydration and anticoagulant therapy. Five of the 7 cases presented with CVT during early pregnancy, among which 1 was discharged after dilation and curettage followed by anticoagulant therapy, 2 received endovascular thrombolysis after which one was discharged and the other one left with right hemiparesis and 2 patients died. Among the 17 patients presented with CVT during puerperium, 10 received anticoagulant therapy after which 4 were fully recovered, 5 left with functional disturbance (3 with hemiplegia, 1 with incomplete motor aphasia and hemiparesis and 1 with blurred vision) and one died. Among the rest 7 cases who underwent endovascular thrombolysis, 3 were fully recovered, 3 left with functional impairment (1 with blind and headache and 2 with hemiplegia), and one died. Altogether, there were 14 patients underwent systemic anticoagulant therapy after which 7 were fully recovered, 5 left with dysfunction and 2 died. Among the 10 cases received endovascular thrombolysis, 4 were fully recovered, 4 remained some dysfunction and 2 died. CONCLUSIONS: CVT, mostly presented as superior sagittal sinus thrombosis, are more common in puerperium than during pregnancy and DSA is the golden standard for the diagnosis of CVT. Anticoagulant therapy and endovascular thrombolysis are effective in the treatment of CVT, but may left the patients with functional disturbance or even death. Prompt diagnosis and treatment ensure a better outcome for pregnant women complicated with CVT.

Diagnostic value of circulating methylated Septin-9 as a biomarker for colorectal cancer:a Meta-analysis study / 中国免疫学杂志

Objective:A meta-analysis was use to systematically assess the diagnostic value of Septin-9 in Colorectal cancer. Methods:Literature fulfilling the criteria was searched in PubMed, Foreign Medical Journals Platform, Ovid, CNKI, CBM, WanFang and VIP Databases from inception to Jan. 2017. Literatures were strictly screened according to the inclusion and exclusion cri-teria. Study quality was assessed in terms of the Quality Assessment of Diagnostic Accuracy Studies ( QUADAS) checklist. A bivariate Meta-analysis model was employed to assess the pooled accuracy,and study heterogeneity was evaluated via Cochran-Q and I2 tests;subgroup analysis and sensitivity analysis were conducted to deeply trace the sources of heterogeneity;publication bias was judged by Deek′s funnel plot. Results:A total of 11 studies were included. Analysis of methylated Septin-9 achieved a pooled sensitivity of 0. 70 (95%CI:0. 67-0. 72),specificity of 0. 91 (95%CI:0. 90-0. 92),and DOR of 28. 76(95%CI:17. 70-46. 75),corresponding to an AUC of 0. 9221. Heterogeneity test suggested that there was obvious heterogeneity from non-threshold effect. Sensitivity analysis identified one outlier study. Subgroup analysis results showed that the AUC of 1/3 positive to 2/3 positive group was 0. 9397 versus 0. 8265,and the AUC of the Asian population group to the Caucasian population group was 0. 9368 versus 0. 9210. Funnel plot ( Deek′s) revealed no publication bias. Conclusion:Our data indicate that circulating methylated Septin-9 seemed to harbor a relatively high accuracy in conforming colorectal cancer,and might be popularized as a routine biomarker for colorectal cancer detection.

Diagnostic value of circulating methylated Septin-9 as a biomarker for colorectal cancer:a Meta-analysis study / 中国免疫学杂志

Objective:A meta-analysis was use to systematically assess the diagnostic value of Septin-9 in Colorectal cancer. Methods:Literature fulfilling the criteria was searched in PubMed, Foreign Medical Journals Platform, Ovid, CNKI, CBM, WanFang and VIP Databases from inception to Jan. 2017. Literatures were strictly screened according to the inclusion and exclusion cri-teria. Study quality was assessed in terms of the Quality Assessment of Diagnostic Accuracy Studies ( QUADAS) checklist. A bivariate Meta-analysis model was employed to assess the pooled accuracy,and study heterogeneity was evaluated via Cochran-Q and I2 tests;subgroup analysis and sensitivity analysis were conducted to deeply trace the sources of heterogeneity;publication bias was judged by Deek′s funnel plot. Results:A total of 11 studies were included. Analysis of methylated Septin-9 achieved a pooled sensitivity of 0. 70 (95%CI:0. 67-0. 72),specificity of 0. 91 (95%CI:0. 90-0. 92),and DOR of 28. 76(95%CI:17. 70-46. 75),corresponding to an AUC of 0. 9221. Heterogeneity test suggested that there was obvious heterogeneity from non-threshold effect. Sensitivity analysis identified one outlier study. Subgroup analysis results showed that the AUC of 1/3 positive to 2/3 positive group was 0. 9397 versus 0. 8265,and the AUC of the Asian population group to the Caucasian population group was 0. 9368 versus 0. 9210. Funnel plot ( Deek′s) revealed no publication bias. Conclusion:Our data indicate that circulating methylated Septin-9 seemed to harbor a relatively high accuracy in conforming colorectal cancer,and might be popularized as a routine biomarker for colorectal cancer detection.

Infantile hepatic hemangioendothelioma: a clinicopathologic study in a Chinese population.

AIM: To investigate whether the clinicopathologic features of infantile hemangioendothelioma (IHE) of the liver in a Chinese population are similar to the features observed in other races. METHODS: The clinical data, radiological findings, histopathological changes and outcome of 12 cases of IHE diagnosed by the Department of Pathology, West China Hospital over the last 10 years were analyzed retrospectively. Immunohistochemical studies were carried out using antibodies against CD31, CD34, Factor VIII, cytokeratin 8 and cytokeratin 18. RESULTS: The 12 patients were aged from fetal to 5 years (three males and nine females). The tumor was presented with different clinical manifestations, mainly as an asymptomatic, palpable, upper abdominal mass, except for the two fetuses who were detected antenatally by ultrasound. In one patient, this presentation was accompanied by an initial severe pneumothorax. No symptoms of congestive heart failure were present and neither congenital abnormalities nor vascular tumors in the skin or other organs were found. Laboratory abnormalities included leukocytosis (40%), anemia (60%), thrombocytosis (60%), hyperbilirubinemia (16.7%), abnormal liver function (50%) and increased α-fetoprotein (80%). Based on radiological findings and gross specimens, the tumor presented as a solitary lesion or a multifocal space-occupying lesion. The tumor size ranged from 5.0 cm × 3.5 cm × 2.0 cm to 13.8 cm × 9.0 cm × 7.7 cm, and the 0.2-1.1 cm nodules were diffusely distributed within the multifocal tumor. Seven cases were surgically resected, three cases underwent biopsy and the two fetuses were aborted. Histologically, nine cases were classified as type I and three as type II, presenting aggressive morphologic features, immature vessels, active mitosis and necrosis. An inflammatory component, predominantly eosinophilic granulocytes, sometimes obscured the nature of the tumor. Ten patients are alive after a follow-up of 1-9 years. Based on immunohistochemistry, the endothelial cells in all cases were positive for CD31, CD34 and polyclonal factor VIII antigen, whereas the scattered hyperplasia bile ducts were positive for cytokeratin 8 and cytokeratin 18. CONCLUSION: The clinical manifestations of IHE are non-specific. There is no significant correlation between histological type and prognosis. The clinicopathologic features of IHE in Chinese patients may provide a clue to further evidence-based studies.