Pharmacokinetic and pharmacodynamic evaluation study of etomidate: a randomized, open-label, 2-period crossover study in healthy Chinese subjects.

Etomidate is a sedative and hypnotic drug through intravenous administration that act on the central nervous system through GABA (Gamma-Amino Butyric Acid) receptors, which is widely used in anesthesia induction and maintenance and long-term sedation in severe patients. The study aimed to evaluate the pharmacokinetic and pharmacodynamic properties of two etomidate fat emulsions after administration through the intravenous infusion pump in healthy Chinese subjects. A randomized, open-label, 2-period crossover study was performed in 52 healthy subjects. The wash-out period was 7 days. Blood samples and pharmacodynamic index values were collected at the specified time points. Etomidate concentrations were measured using validated liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were analyzed using a non-compartment model method. Pharmacodynamic parameters were calculated using pharmacodynamic index values. The study also evaluated the safety of the etomidate. Both the pharmacokinetic parameters and pharmacodynamic parameters result of the test and reference formulation were very similar. The 90% confidence intervals (CI) of the geometric least-squares mean (GLSM) ratios of the test to reference formulation were 91.33-104.96% for the maximum plasma concentration (Cmax), 97.21-102.03% for the area under the plasma concentration time curve from time 0 to the time of the last measurable concentration (AUC0-t), and 97.22-102.33% for the area under the plasma concentration time curve from time 0 to infinity (AUC0-∞). Meanwhile, the 90% CI of the GLSM ratios of the test to reference formulation were 102.28-110.69% for the minimal BIS value (BISmin), 99.23-101.17% for the area under the BIS time curve from time 0-60 min after administration (BISAUC0-60 min), respectively. The 90% CI of these pharmacokinetic and pharmacodynamic parameters all fall in the accepted bioequivalence range of 80.00-125.00%. No serious adverse events occurred during the study. This study has shown that the etomidate fat emulsion test and reference formulation had similar pharmacokinetic and pharmacodynamic characteristics in vivo. The two formulations exhibited good safety and well-tolerance.Clinical trials registration number: http://www.chinadrugtrials.org.cn/index.html . # CTR20191836.

Helicobacter pylori infection in Xinjiang Uyghur Autonomous Region: Prevalence and analysis of related factors.

BACKGROUND: 14C urea breath test (14C UBT) and immunohistochemical staining (IHC) are widely used for detection Helicobacter pylori (H. pylori) infection with different sensitivity, and there is a difference in H. pylori infection rate in Uyghur and Han ethnic groups. Both need large cohort studies to evaluate the differences more accurately. AIM: To analyze the difference between 14C UBT and IHC for H. pylori detection in Xinjiang Uyghur Autonomous Region and the difference between Uyghur and Han populations. METHODS: There were 3944 cases of H. pylori infection detected by both IHC and 14C UBT at the same time (interval < 1 wk, with sampling site including gastric antrum, selected from 5747 patients). We compared the sensitivity of 14C UBT and IHC. We also compared 555 pairs of Han/Uyghur cases (completely matched for gender and age) for their H. pylori infection rates. The overall H. pylori infection rate of all 5747 cases and the correlation with other clinicopathological data were also further analyzed. SPSS V23.0 software was used for statistical analysis. RESULTS: The sensitivity was 94.9% for 14C UBT and 65.1% for IHC, which was a significant difference (n = 3944, P < 0.001). However, among those cases negative for H. pylori by 14C UBT (detection value ≤ 100), 4.8% were positive by IHC. Combining both methods, the overall H. pylori infection rate was 48.6% (n = 5747), and differences in gender, age group, ethnicity and region of residence significantly affected the H. pylori positive rates. According to age group (Han/Uyghur), the positive rates were ≤ 30 years (62.2%/100.0%), 31-40 years (45.2%/85.7%), 41-50 years (47.2%/79.2%), 51-60 years (44.6%/76.1%), 61-70 years (40.9%/68.2%), 71-80 years (41.7%/54.1%) and ≥ 81 years (42.9%/NA). The H. pylori infection rates of Han/Uyghur paired cases were 41.4% and 73.3%, which was a significant difference (P < 0.001) (555 pairs). H. pylori positivity was significantly related to moderate-severe grade 2-3 chronic/active gastritis and intestinal metaplasia (all P < 0.05). CONCLUSION: The sensitivity of 14C UBT was significantly higher, but combined application can still increase the accuracy. The prevention H. pylori should be emphasized for Uygur and young people.

Artificial intelligence pathway search to resolve catalytic glycerol hydrogenolysis selectivity.

The complex interaction between molecules and catalyst surfaces leads to great difficulties in understanding and predicting the activity and selectivity in heterogeneous catalysis. Here we develop an end-to-end artificial intelligence framework for the activity prediction of heterogeneous catalytic systems (AI-Cat method), which takes simple inputs from names of molecules and metal catalysts and outputs the reaction energy profile from the input molecule to low energy pathway products. The AI-Cat method combines two neural network models, one for predicting reaction patterns and the other for providing the reaction barrier and energy, with a Monte Carlo tree search to resolve the low energy pathways in a reaction network. We then apply AI-Cat to resolve the reaction network of glycerol hydrogenolysis on Cu surfaces, which is a typical selective C-O bond activation system and of key significance for biomass-derived polyol utilization. We show that glycerol hydrogenolysis features a huge reaction network of relevant candidates, containing 420 reaction intermediates and 2467 elementary reactions. Among them, the surface-mediated enol-keto tautomeric resonance is a key step to facilitate the primary C-OH bond breaking and thus selects 1,2-propanediol as the major product on Cu catalysts. 1,3-Propanediol can only be produced under strong acidic conditions and high surface H coverage by following a hydrogenation-dehydration pathway. AI-Cat further discovers six low-energy reaction patterns for C-O bond activation on metals that is of general significance to polyol catalysis. Our results demonstrate that the reaction prediction for complex heterogeneous catalysis is now feasible with AI-based atomic simulation and a Monte Carlo tree search.

Methanol Synthesis from CO2/CO Mixture on Cu-Zn Catalysts from Microkinetics-Guided Machine Learning Pathway Search.

Methanol synthesis on industrial Cu/ZnO/Al2O3 catalysts via the hydrogenation of CO and CO2 mixture, despite several decades of research, is still puzzling due to the nature of the active site and the role of CO2 in the feed gas. Herein, with the large-scale machine learning atomic simulation, we develop a microkinetics-guided machine learning pathway search to explore thousands of reaction pathways for CO2 and CO hydrogenations on thermodynamically favorable Cu-Zn surface structures, including Cu(111), Cu(211), and Zn-alloyed Cu(211) surfaces, from which the lowest energy pathways are identified. We find that Zn decorates at the step-edge at Cu(211) up to 0.22 ML under reaction conditions with the Zn-Zn dimeric sites being avoided. CO2 and CO hydrogenations occur exclusively at the step-edge of the (211) surface with up to 0.11 ML Zn coverage, where the low coverage of Zn (0.11 ML) does not much affect the reaction kinetics, but the higher coverages of Zn (0.22 ML) poison the catalyst. It is CO2 hydrogenation instead of CO hydrogenation that dominates methanol synthesis, agreeing with previous isotope experiments. While metallic steps are identified as the major active site, we show that the [-Zn-OH-Zn-] chains (cationic Zn) can grow on Cu(111) surfaces under reaction conditions, which suggests the critical role of CO in the mixed gas for reducing the cationic Zn and exposing metal sites for methanol synthesis. Our results provide a comprehensive picture on the dynamic coupling of the feed gas composition, the catalyst active site, and the reaction activity in this complex heterogeneous catalytic system.

Primary hepatoid adenocarcinoma of the lung in Yungui Plateau, China: A case report.

BACKGROUND: Hepatoid adenocarcinoma (HAC) occurs in extrahepatic organs such as the gastrointestinal tract, testes, ovaries, lungs, mediastinum and pancreas, and frequently produces α-fetoprotein (AFP). HAC of the lung (HAL) is rare, characterized by difficult treatment and poor prognosis. There are no reports of HAL in Yunnan-Guizhou Plateau, China. CASE SUMMARY: A 60-year-old male patient was clinically diagnosed with HAL pT3N0M0, stage IIB. Chest computed tomography revealed a 7.5 cm × 7.2 cm soft tissue mass located in the right lung upper lobe and the adjacent superior mediastinum. Right upper lobectomy was performed. The diagnosis of HAL was confirmed by pathological examination, and the patient received paclitaxel and carboplatin as adjuvant chemotherapy after surgery. CONCLUSION: Clinical manifestations, pathological features, imaging findings, auxiliary examination, and treatment planning of HAL are presented to help clinicians improve their diagnosis and treatment.

Significance of HER2 protein expression and HER2 gene amplification in colorectal adenocarcinomas.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is an oncogenic driver, and a well-established therapeutic target in breast and gastric cancers. While the role of HER2 as a prognostic biomarker in colorectal adenocarcinomas (CRCs) remains uncertain, its relevance as a therapeutic target has been established. We undertook the present study to evaluate the frequency of HER2 expression in CRC and to correlate it with various clinicopathological variables. AIM: To correlate HER2 protein expression and HER2 gene amplification with clinicopathological features and survival in surgically resected CRC. METHODS: About 1195 consecutive surgically resected CRCs were analyzed by immunohistochemical staining (IHC) to assess HER2 protein expression, and 141 selected tumors were further evaluated by fluorescence in situ hybridization (FISH) to assess HER2 gene amplification. Follow-up information was available for 1058 patients, and using this information we investigated the prevalence of HER2 protein overexpression and gene amplification in a large series of surgically resected CRCs, and evaluated the relationship between overexpression and clinicopathological parameters and prognosis. RESULTS: HER2 IHC scores of 3+, 2+, 1+, and 0 were seen in 31 (2.6%), 105 (8.8%), 475 (39.7%), and 584 (48.9%) tumors, respectively. HER2 gene amplification was seen in 24/29 tumors with an IHC score of 3+ (82.8%; unreadable in 2/31), 12/102 tumors with an IHC score of 2+ (11.8%; unreadable in 2/104), and 0 tumors with IHC score of 1+ (0/10). HER2 gene amplification was seen in 36/1191 tumors (3.0%; unreadable in 4/1195). Among the tumors with HER2 IHC scores of 3+ and 2+, the mean percentage of tumor cells with positive IHC staining was 90% (median 100%, range 40%-100%) and 67% (median 75%, range 5%-95%), respectively (P < 0.05). Among tumors with IHC scores of 2+, those with HER2 gene amplification had a higher number of tumors cells with positive IHC staining (n = 12, mean 93%, median 95%, range 90%-95%) than those without (n = 90, mean 70%, median 50%, range 5%-95%) (P < 0.05). HER2 gene status was significantly associated with distant tumor metastasis and stage (P = 0.028 and 0.025). HER2 protein overexpression as measured by IHC or HER2 gene amplification as measured by FISH was not associated with overall survival (OS) or disease-specific survival for the overall group of 1058 patients. However, further stratification revealed that among patients with tubular adenocarcinomas who were 65 years old or younger (n = 601), those exhibiting HER2 gene amplification had a shorter OS than those without (mean: 47.9 mo vs 65.1 mo, P = 0.04). Among those patients with moderately to poorly differentiated tubular adenocarcinomas, those with positive HER2 tumor IHC scores (2+, 3+) had a shorter mean OS than those with negative HER2 IHC scores (0, 1+) (47.2 mo vs 64.8 mo, P = 0.033). Moreover, among patients with T2 to T4 stage tumors, those with positive HER2 IHC scores also had a shorter mean OS than those with negative HER2 IHC scores (47.1 mo vs 64.8 mo, P = 0.031). CONCLUSION: HER2 protein levels are correlated with clinical outcomes, and positive HER2 expression as measured by IHC confers a worse prognosis in those patients 65 years old or younger with tubular adenocarcinomas.

Involvement of bone marrow in lymphoma: pathological investigation in a single-center from northern China.

OBJECTIVES: This study aimed to evaluate key features of bone marrow trephine biopsy (BMT) involvement of lymphoma in Northern China. METHODS: 950 cases were assessed for the occurrence of bone marrow involvement and architectural features including volume percentage, involvement pattern (diffuse, nodular, focal, para trabecular, or interstitial), and presence/absence of background changes (granuloma, stromal fibrosis or necrosis). Correlations with bone marrow aspirate (BMA) and flow cytometry (FCM) findings were made in a subset of paired cases (359 BMA and 364 FCM). RESULTS: 153 (16.1%) cases involved BMT. The most frequent type was mantle cell lymphoma (28/153, 18.3%). Architectural features were similar to previous studies except that diffuse large B-cell lymphoma (DLBCL) preferred focal pattern (16/22 cases, 72.7%) most of all. BMA and BMT agreed in 84.1% of cases (302 of 359: 277 both negative, 25 both positive), while FCM and BMT agreed in 80.8% of cases (294 of 364: 242 both negative, 52 both positive). Both varied widely among different subgroups. CONCLUSIONS: Occurrence of BMT involvement by lymphoma in Northern China is relatively low. The volume percentage, distribution patterns and background changes may be useful pointers towards a particular lymphoma type in Chinese. FCM is more sensitive and reliable than BMA in China.

Interleukin-1ß-mediated suppression of microRNA-101 and upregulation of enhancer of zeste homolog 2 is involved in particle-induced lung cancer.

Lung cancer may be a result of complex factors. Small mineral particle is the well-known inducer of lung cancer. Previous study revealed the high morbidity of lung cancer in Xuan Wei in China, and the main cause of lung cancer is the use of smoky coal there. And it is generally accepted that chronic inflammation induced by small mineral particle may be a cause of lung cancer. But the relationship between chronic lung inflammation and lung cancer is largely unknown. In the present study, we found that silica particle was able to induce the secretion of interleukin-1ß from a Xuan Wei lung cancer cell line, XWLC-05. At the same time, microRNA-101 (mir-101) was found to be downregulated by the treatment of silica particle. Interestingly, the interleukin 1 receptor antagonist and interleukin-1ß antibody can reduce silica particle-induced downregulation of mir-101. Twenty-four Xuan Wei lung tumor tissues were collected to detect the expression level of mir-101 and enhancer of zeste homolog 2 (EZH2), which is the potential target of mir-101. The results showed that mir-101 was down-regulated and EZH2 were upregulated. Subsequently, the roles of mir-101 and EZH2 in tumor growth and progression in vitro were tested. Overexpression of mir-101 mimics was able to suppress the expression of EZH2 in XWLC-05 cells. And this resulted in the inhibited tumor cell growth and attenuated cell migration. The results in the present study showed that particle can induce the secretion of interleukin-1ß. Interleukin-1ß subsequently induces the downregulation of mir-101, which may result in the upregulated level of EZH2, and occurrence of lung cancer. We for the first time proposed the role interleukin-1ß-mir-101-EZH2 axes in the particle-induced lung cancer. Further study may be needed to decipher the detailed mechanism involved.

Downregulation of miR-193a-5p correlates with lymph node metastasis and poor prognosis in colorectal cancer.

AIM: To investigate the correlation of miR-193a-5p with lymph node metastasis and postoperative survival of colorectal cancer (CRC) patients. METHODS: A total of 304 formalin-fixed, paraffin-embedded specimens (69 paired cancer and normal tissues, 55 primary tumors of stage III CRC and matched lymph nodes, and 56 primary tumors of stage II CRC) were included in this study. The relative expression levels of miR-193a-5p in the normal mucosa, primary cancer, and metastatic lymph node lesions were measured by quantitative real-time reverse transcriptase polymerase chain reaction. We evaluated the association of its expression with colorectal cancer lymph node metastasis, clinicopathological factors, and patient survival. RESULTS: The relative expression level of miR-193a-5p was significantly lower in CRC tissues than in the normal mucosa (P = 0.0060). The expression levels of miR-193a-5p were lower in primary CRC tissues with lymph node metastases than in those without metastases (P = 0.0006), and decreased expression of miR-193a-5p correlated with advanced lymph node metastatic stage (P = 0.0007). Kaplan-Meier analysis showed that patients with low miR-193a-5p expression had decreased disease-free survival (DFS) (P = 0.0026) and poor overall survival (OS) (P = 0.0003). Interestingly, for the group of patients with lymph node metastases, miR-193a-5p expression was also related to survival. Patients with low miR-193a-5p expression had decreased DFS (P = 0.0262) and poor OS (P = 0.0230). Moreover, multivariate analysis indicated that downregulation of miR-193a-5p was an independent predictor of poor OS. CONCLUSION: Downregulation of miR-193a-5p correlates with lymph node metastasis and poor survival of CRC. miR-193a-5p may be a useful biomarker for CRC diagnosis, metastasis and prognosis prediction.

Clinical value of real time elastography in patients with unexplained cervical lymphadenopathy: quantitative evaluation.

Ultrasonography is non-invasive and can give useful clues in the diagnosis of cervical lymphadenopathy, However, differential diagnosis is difficult in some situations even combined with color Doppler imaging. The present study was conducted to evaluate the clinical value of real time elastography in patients with unexplained cervical lymphadenopathy using a quantitative method. From May 2011 to February 2012, 39 enlarged lymph nodes from 39 patients with unexplained cervical lymphadenopathy were assessed. All the patients were examined by both B-mode ultrasound, color Doppler flow imaging and elastography. The method of analyzing elasto-graphic data was the calculation of the 10 parametres ("mean", "sd", "area%", "com", "kur", "ske", "con", "ent", "idm", "asm") offered by the software integrated into the Hitachi system. The findings were then correlated with the definitive tissue diagnosis obtained by lymph node dissection or biopsy. Final histology revealed 10 cases of metastatic lymph nodes, 11 cases of lymphoma, 12 cases of tuberculosis and 6 cases of nonspecific lymphadenitis. The significant distinguishing features for conventional ultrasound were the maximum short diameter (p=0.007) and absent of echogenic hilum (p=0.0293). The diagnostic accuracy was 43.6% (17/39 cases) and there were 17 patients with equivocal diagnosis. For elastography, "mean" (p=0.003), "area%" (p=0.009), "kurt" (p=0.0291), "skew" (p=0.014) and "cont" (p=0.012) demonstrated significant differences between groups. With 9 of the 17 patients with previous equivocal diagnoses (52.9%) definite and correct diagnoses could be obtained. The diagnostic accuracy for conventional ultrasound combined elastography was 69.2% (27/39 cases). There were differences in the diagnostic sensitivity of the two methods (p=0.0224). Ultrasound combined with elastography demonstrated higher rates of conclusive and accurate diagnoses in patients with unexplained cervical lymphadenopathy than conventional ultrasound. The quantitative program showed good correlation with the pathology of different lymph node diseases.

[Clinical characteristics and prognosis analysis of patients with LMP-1 positive Hodgkin's lymphoma after EBV infection].

This study was purposed to investigate the expression of latent membrane protein 1 (LMP-1) and CD68 in Hodgkin's lymphoma (HL) patients with EB virus infection and to analyze the relation of LMP-1 expression and CD68(+) tumor-associated macrophage count with clinical features and prognosis of HL patients. The expression of LMP1 and count of CD68(+) TAM were detected by immunohistochemical staining in tissue specimens of 72 HL patients; their correlation with clinical features and prognosis of HL patients was analyzed by using statistical method. The results showed that among tissue specimens of 72 HL patients, the positive rate of LMP-1 expression was 18.1% (13/72), the CD68(+) TAM count was more higher in LMP-1 positive expression [250 of CD68(+) TAM/high power field (hpf) is used as demarcation point] (P = 0.003). The statistical analysis showed that the LMP-1 positive expression was more observed in mixed type HL patients (P = 0.000); the positive rate of LMP-1 expression was much high in HL patients with albumin <40 g/L and age ≥ 45 years (P < 0.05). There was no relation of LMP-1 expression and CD68(+) TAM count with the short term therapeutic efficacy of HL patients, but the overall survival time of LMP-1 positive patients among patients followed-up for ≥ 5 years was short (P < 0.05). Moveover, no correlation of CD68(+) TAM count with the overall survival time of HL patients was found. It is concluded that the high count of CD68(+) TAM is more observed in LMP-1 positive expression of HL tissue, the LMP-1 expression states relates both with the pathological types, age and albumin level of patient with HL. The HL patients with LMP-1 positive expression have poor prognosis, suggesting that LMP-1 may be a new prognostic marker for HL patients.

[Immunohistochemical patterns of follicular dendritic cell meshwork and Ki-67 in small B-cell lymphomas].

OBJECTIVE: To identify the immunohistochemical patterns of follicular dendritic cell (FDC) meshwork and Ki-67 labeling index in small B-cell lymphomas (SBLs) and their significance in differential diagnosis. METHODS: Sixty-eight cases of SBLs were included collected from November 2008 to June 2012. The patterns of FDCs and Ki-67 expression were studied on paraffin sections by CD21, CD23 and Ki-67 immunohistochemistry. The characteristic staining patterns of FDCs and Ki-67 expression among different SBLs were analyzed statistically. RESULTS: The age of SBL patients ranged from 28 to 85 years with a mean of 55.2 years. The male to female ratio was 1.2:1. Fifty-five cases involved only lymph nodes (80.9%), and the remaining cases involved multiple extra-nodal sites. Histological classification of the cases was made according to the 2008 WHO lymphoma classification criteria: 22 were low-grade follicular lymphomas (FLs, including grade 1 and grade 2), 19 marginal zone lymphomas (MZLs), 17 mantle cell lymphomas (MCLs), and 10 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLLs). FDC meshwork limited to the central part of neoplastic follicles was characteristic for FL (90.9%, 20/22). The germinal center FDC meshwork was destroyed primarily at periphery in MZL (14/19). The absence or scattered FDC clusters were typical of SLL/ CLL. Irregular FDC was seen in 7/17 of MCL, while 7/17 MCL displayed FDC pattern similar to that of CLL/SLLs. The pattern of FDCs was a significantly diagnostic feature in distinguishing the four types of SBLs (P < 0.01). Ki-67 was also a statistically significant parameter (P < 0.05) with decreasing labeling index as the following: MCL, FL, SLL and MZL. Ki-67 showed scattered pattern in germinal centers with loss of polarity in FLs. MZL presented uniformly scattered positive pattern in interfollicullar areas. Ki-67 staining was uniform in MCL, but its labeling index varied from 5% to 90%. The Ki-67 index was higher in the morphological "proliferation centers" of all CLL/SLLs. CONCLUSION: Immunohistochemical staining patterns of FDC meshworks and Ki-67 labeling index offer a significant discriminatory power in the differential diagnoses among SBLs.

Clinical and laboratory characteristics of systemic anaplastic large cell lymphoma in Chinese patients.

BACKGROUND: Systemic anaplastic large cell lymphoma (S-ALCL) is a rare disease with a highly variable prognosis and no standard chemotherapy regimen. Anaplastic lymphoma kinase (ALK) has been reported as an important prognostic factor correlated with S-ALCL in many but not all studies. In our study, we retrospectively analyzed 92 patients with S-ALCL from the Peking University Lymphoma Center for clinical and molecular prognostic factors to make clear the role of ALK and other prognostic factors in Han Chinese S-ALCL. RESULTS: The majority of Chinese S-ALCL patients were young male patients (median age 26, male/female ratio 1.7) and the median age was younger than previous reports regardless of ALK expression status. The only statistically significant different clinical characteristic in S-ALCL between ALK positive (ALK+) and ALK negative (ALK-) was age, with a younger median age of 22 for ALK+ compared with 30 for ALK-. However, when pediatric patients (≤ 18) were excluded, there was no age difference between ALK+ and ALK-. The groups did not differ in the proportion of males, those with clinical stage III/IV (49 vs 51%) or those with extranodal disease (53 vs 59%). Of 73 evaluable patients, the 3-year and 5-year survival rates were 60% and 47%, respectively. Univariate analysis showed that three factors: advanced stage III/IV, lack of expression of ALK, and high Ki-67 expression, were associated with treatment failure in patients with S-ALCL. However, ALK expression correlated with improved survival only in patients younger than 14 years, while not in adult patients. In multivariate analysis, only clinical stage was an independent prognostic factor for survival. Expressions of Wilms tumor 1 (WT1) and B-cell lymphoma 2 protein (BCL-2) correlated with the expression of ALK, but they did not have prognostic significance. High Ki-67 expression was also a poor prognostic factor. CONCLUSIONS: Our results show that ALK expression alone is not sufficient to determine the outcome of ALCL and other prognostic factors must be considered. Clinical stage is an independent prognostic factor. Ki-67 expression is a promising prognostic factor.

Synchronous pulmonary squamous cell carcinoma and mantle cell lymphoma of the lymph node.

Synchronous occurrence of pulmonary squamous cell carcinoma and malignant lymphoma of the lymph node is not reported in the literature. We report a case of pulmonary squamous cell carcinoma coexisting with a mantle cell lymphoma involving cervical and mediastinal lymph node. It is important to recognize this synchronous occurrence histopathologically and to be aware of the existence of "in situ" MCL.

[Anaplastic lymphoma kinase gene abnormality and the expression of its fusion protein in primary systemic anaplastic large cell lymphoma].

OBJECTIVE: To study the expression of anaplastic lymphoma kinase (ALK) and chromosome breakage of the anaplastic lymphoma kinase (ALK) gene retrospectively and to investigate their possible value as indicators of prognosis in primary systemic anaplastic large cell lymphomas (S-ALCL). METHODS: Twenty-eight cases of S-ALCL were collected from the Lymphoma Lab, the Department of Pathology, Peking University Health Science Center and Beijing Children's Hospital. The morphologic characteristics were studied under light microscope, and essential immunohistochemical staininings (IHC) were performed and reviewed to confirm the diagnosis of S-ALCL. ALK-1 monoclonal antibody was used to assess ALK fusion protein expression, and EnVision method was used in IHC. Locus specific interphase fluorescence in situ hybridization (LSI-FISH) was also performed on the neoplastic cells using paraffin-embedded tissues to detect ALK gene abnormality. RESULTS: ALK-1 protein was expressed in 19 of the 28 cases. In 14 ALCL cases, ALK gene breakage was detected by LSI-FISH, using a dual-color break-apart ALK gene DNA (LSI-ALK) probe. Of the other 14 cases which did not show ALK gene breakage, 5 showed 2 copies of ALK gene as normal, and 9 showed multi-copies of ALK gene. Of all the 28 cases, 22 had complete follow-up materials. Sixteen survived and 6 died, their survival time ranged from 0.5 to 36.0 months, and the survival time on average was 12.8 months, cumulative proportion survival rate was 73.9% in the 1st year. Those cases showing multi-copies of ALK gene might have the worst outcome, with only 47.6% of cumulative proportion survival rate in the 1st year. CONCLUSION: IHC detection for ALK fusion protein is important to the diagnosis of S-ALCL. ALK gene breakage detected by interphase LSI-FISH might not be always consistent with abnormal expression of ALK fusion protein. Complex abnormalities of ALK gene exist in S-ALCL cases, and different types of ALK gene might lead to different clinical outcome. Those cases with multi-copies of ALK gene probably have the poorest prognosis.