Risk factors analysis and prediction model construction of submucosal deep infiltration of early colorectal tumor / 中华肿瘤杂志

Objective: To investigate the risk factors for the development of deep infiltration in early colorectal tumors (ECT) and to construct a prediction model to predict the development of deep infiltration in patients with ECT. Methods: The clinicopathological data of ECT patients who underwent endoscopic treatment or surgical treatment at the Cancer Hospital, Chinese Academy of Medical Sciences from August 2010 to December 2020 were retrospectively analyzed. The independent risk factors were analyzed by multifactorial regression analysis, and the prediction models were constructed and validated by nomogram. Results: Among the 717 ECT patients, 590 patients were divided in the within superficial infiltration 1 (SM1) group (infiltration depth within SM1) and 127 patients in the exceeding SM1 group (infiltration depth more than SM1). There were no statistically significant differences in gender, age, and lesion location between the two groups (P>0.05). The statistically significant differences were observed in tumor morphological staging, preoperative endoscopic assessment performance, vascular tumor emboli and nerve infiltration, and degree of tumor differentiation (P<0.05). Multivariate regression analysis showed that only erosion or rupture (OR=4.028, 95% CI: 1.468, 11.050, P=0.007), localized depression (OR=3.105, 95% CI: 1.584, 6.088, P=0.001), infiltrative JNET staging (OR=5.622, 95% CI: 3.029, 10.434, P<0.001), and infiltrative Pit pattern (OR=2.722, 95% CI: 1.347, 5.702, P=0.006) were independent risk factors for the development of deep submucosal infiltration in ECT. Nomogram was constructed with the included independent risk factors, and the nomogram was well distinguished and calibrated in predicting the occurrence of deep submucosal infiltration in ECT, with a C-index and area under the curve of 0.920 (95% CI: 0.811, 0.929). Conclusion: The nomogram prediction model constructed based on only erosion or rupture, local depression, infiltrative JNET typing, and infiltrative Pit pattern has a good predictive efficacy in the occurrence of deep submucosal infiltration in ECT.

Research Status of Traditional Chinese Medicine in Treating Gastric Cancer and Precancerous Lesion of Gastric Cancer by Regulating Autophagy / 中国实验方剂学杂志

Gastric cancer is one of the most common malignant tumors in the digestive system， and precancerous lesion of gastric cancer （PLGC） represents a long-term stage in the process of malignant development of normal gastric mucosa into gastric cancer. Gastric cancer and precancerous lesions are difficult to cure clinically， leaving poor prognosis and a serious negative impact on the quality of daily life of patients. In recent years， studies on cell autophagy have been at the forefront of the natural life science. Regulating autophagy to treat precancerous lesions and prevent gastric cancer has become nowadays a hot topic. Autophagy is a process in which cells enclose some redundant or damaged cytoplasm， proteins and organelles to form autophagosomes， and bind to lysosomes to degrade the contents. Autophagy has bidirectional effect on different cells and different stages of the same cell. Autophagy at a lower level can kill cancer cells， while autophagy can promote the growth and proliferation of cancer cells under stress conditions such as hypoxia， hunger and infection， or when autophagy clears damaged proteins in cells and organelle function is abnormal. Traditional Chinese medicine（TCM）， which has low toxicity and easy acceptance by patients， has a positive effect on the treatment of gastric cancer and PLGC. At present， studies on the prevention and treatment of gastric cancer and PLGC by TCM have been carried out in depth with cell autophagy as the breakthrough point. More and more research results have confirmed that TCM can regulate the autophagy process of gastric cancer cells and play an anti-tumor role by interfering with various autophagy related genes， signal pathways and organelles. This paper summarizes the studies on the regulation of cell autophagy by TCM in the treatment of gastric cancer and precancerous lesions， so as to provide references for future studies on the regulation of autophagy by TCM.

Molecular Characterization of La Protein in a Mouse Acute Hepatitis Model / 中国药学杂志

OBJECTIVE: To explore the role of La protein in acute hepatitis B virus (HBV) by establishing a mouse model. METHODS: We constructed an acute hepatitis B virus model by hydrodynamics-based injection of plasmid pAAV/HBV1.2 containing 1.2 times HBV genome. The expression levels of HBV DNA, HBsAg and HBeAg in serum were detected by RT-PCR and ELISA, respectively. HBcAg in liver tissue were assayed by immunohistochemical staining.The level of ALT was detected by bioluminescence. Pathological changes in liver carried by Hematoxylin and eosin (HE) staining. RT-PCR, Western blot and ELISA were used to detect the changes of mRNA level and protein expression level of La protein. RESULTS: The levels of HBV DNA, HBsAg and HBeAg in the serum of mice, and the percentage of HBcAg-positive hepatocytes in liver tissues was up to 3.66% at day 5 showed that the mouse model of acute HBV was successfully constructed. The level of serum ALT and HE results showed that the liver damage was serious after the model was established, and then dropped sharplyand returned to normal. The mRNA level of La protein in the liver of the mice indicates that the level of La protein in the model group was generally higher than that in the control group. However, Western bolt results showed that there was no significant difference in intracellular protein levels, but the level of La protein in serum of mice is generally higher thancontrol group, especially on the 7th day (P<0.000 1). CONCLUSION: The acute HBV model was successfully constructed. The level of La protein in this model is related to HBV expression, suggesting that La protein may be involved in the pathogenesis of HBVandbea new marker in diagnosis of HBV.

Effects of USP9X down-regulation on apoptosis and invasion ability of gastric carcinoma AGS cells / 中国病理生理杂志

AIM:To investigate the effects of ubiquitin-specific peptidase 9, X-linked (USP9X) down-regula-tion on apoptosis and invasion ability in gastric carcinoma cells, and to explore its possible molecular mechanisms. METH-ODS:USP9X small interfering RNA (siRNA) and control siRNA were used to be transfected into gastric carcinoma AGS cells. The cells were divided into 3 groups, including untreated AGS group, control siRNA group and USP9X siRNA group. The expression of USP9X at mRNA and protein levels in the AGS cells with different treatments was determined by real-time PCR and Western blot. The cell viability was analyzed by CCK-8 assay. Flow cytometry and Boyden chamber were employed to examine the apoptosis and invasion ability of the AGS cells. RESULTS:USP9X siRNA significantly down-regulated the expression of USP9X at mRNA and protein levels in the AGS cells. Down-regulation of USP9X markedly induced apoptosis and reduced invasion ability of the gastric carcinoma AGS cells. Notably, down-regulation of USP9X sig-nificantly reduced the protein expression of Mcl-1 and MMP-2, but markedly increased the protein level of Bax. CON-CLUSION:USP9X may be a key regulator for apoptosis and invasion in gastric carcinoma.

Effect of androgen on mice tear film stability and Mucins expressions in mice corneal epithelial cells in vivo / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To study in vivo the effect of androgen on mice tear film stability and Mucins expressions in corneal epithelial cells in BALB/ c mice after orchectomy. METHODS: With orchiectomy operation, we set up mice model. And serum androgen concentration of mice was detected by radioimmunoassay. Break - up time ( BUT ) of tear film was tested in the different experimental points. Mice corneal epithelia were peeled and MUC1 and MUC4 mRNA and protein levels were measured by RT-PCR and Western blot. RESULTS: The serum androgen concentration reduced to 0ng/ μ L at 1wk after orchiectomy. The BUT values were 68. 33±12. 86s, 62. 47±3. 75s, 58. 67± 10. 03s, 47. 17±7. 64s, 39. 51±3. 39s, 32. 67±3. 88s and 31. 00±2. 36s in the normal control group, sham group and in orchectomy group at 1, 2, 4, 6 and 8wk, respectively, and the BUTs were significantly shorter in the orchectomy at 2, 4, 6 and 8wk groups than those in the normal control group (all at PCONCLUSION: In vivo, androgen regulates Mucins expressions in mice corneal epithelial cells, makes BUT shorter,and influence the stability of tear film.

Tashinone II A-sulfoacid-natrum elevates the pain threshold through inhibiting nuclear factor kappa B pathway in neuropathic cancer pain.

OBJECTIVE: The purpose of this study was to evaluate the effects of Tashinone II A-sulfoacid-natrum on the pain threshold and potential molecular mechanism for neuropathic cancer pain. METHODS: Forty‑five male Balb/c mice were divided into control group model group and experiment group with each 15. The sciatic nerve muscle plexus of experiment and model group were given injection containing S180 sarcoma cell 2 × 106 mL for each mouse. Mice in the experiment group were given Tashinone II A-sulfoacid-natrum 25 mg/kg once a day intraperitoneal injection. Moreover, mice in the control group were given physiological saline 25 mg/kg, once a day intraperitoneal injection. The mechanical withdraw threshold and thermal withdraw latency were recorded before S180 sarcoma cell injection and in the time point of day 3, 6, 9, 12, and 14. After 14 days treatment, the mice were treated to death and the sciatic nerve CX3CR1 and nuclear factor kappa B (NF‑κB) mRNA was tested by quantitative polymerase chain reaction. RESULTS: Compared with control group, the mechanical and thermal pain threshold of experiment group was significant decreased (P < 0.05). However, compared with the model group, the mechanical, and thermal pain threshold of experiment group was significant elevated in time point of day 3, 6, 9, 12, 14 for mechanical pain threshold and day 9, 12 14 for thermal pain threshold (P < 0.05); the pain threshold for the experiment and model group was decreased in the first 9 days and then elevated gradually. Compared with control group, the CX3CR1 and NF‑κB mRNA relative expression in mice sciatic nerve of experiment group was significant elevated (P < 0.05); but compared with model group, the CX3CR1 and NF‑κB mRNA relative expression of experiment group was significant decreased (P < 0.05). CONCLUSION: Tashinone II A-sulfoacid-natrum can elevates the mechanical and thermal pain threshold through inhibiting the NF‑κB in neuropathic cancer pain rat.

Mechanism of sophocarpine in treating experimental colitis in mice / 中国中药杂志

To study the preventive effect of sophocarpine (Soc) on dextran sulfate sodium (DSS)-induced colitis in mice, in order to analyze the influence of Soc on toll like receptor 4 (TLR4)/mitogen-activated protein kinases (MAPKs) and janus tyrosine kinase 2 signal transducer and activator of transcription 3 (JAK2/STAT3) signal pathways in mice intestinal tissues. The mice was given 2.5% DSS for 6 days to induce the acute colitis model. The Soc-treated group was intraperitoneally injected with sophocarpine 30 mg · kg(-1) · d(-1) since the day before the experiment to the end. The disease activity index (DAI) was assessed everyday, and the colonic morphology and histological damage were observed with HE staining. The mRNA expressions of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were detected by real-time RT-PCR. The changes in key protein kinase p38 mitogen-activated protein kinase (p38MAPK), c-Jun NH2-terminal protein kinase1/2 (JNK1/2), extracellular signal-regulated kinase1/2 (ERK1/2), JAK2, STAT3 in TLR4/MAPKs and JAK2/STAT3 signaling pathways were detected by western blot. The result showed that the model group showed statistical significance in body weight, DAI, colon length and histopathological changes compared with the normal group (P <0.05); however, the Soc-treated group showed significant improvements in the above indexes compared with the model group (P <0.05). TNF-α, IL-1β and IL-6 in the model group was significantly higher than that in the normal group (P <0.05), but lowered in the Soc-treated group to varying degrees (P <0.05). In the normal group, the expressions of TLR4 and the phosphorylation of P38, JNK1/2, JAK2, STAT3 were at low levels; in the model group, the phosphorylation of P38, JNK1/2, JAK2, STAT3 increased; the Soc-treated group showed a decrease in TLR4 expression compared with the model group, with notable declines in the phosphorylation of TLR4, P38, JNK1/2, JAK2, STAT3. These findings indicate that Soc can inhibit TLR4/MAPKs, K2/STAT3 signaling pathway activation, reduce the expression of proinflammatory cytokines TNF-α, IL-1β and IL-6 and relieve inflammatory reactions, so as to effectively prevent experimental colitis.

Comparison Study on Determination of Trace Element Content in Peach Pulp between Wet Digestion Method and Carbonize Acid Dissolution Method / 世界科学技术-中医药现代化

This study was aimed to determine trace elements in Peach pulp . The wet digestion method and car-bonize acid dissolution method were applied to digest the sample, and flame atomic absorption spectroscopy was used to determine the content of trace elements (Fe, Cu, Mn) in Peach pulp . The results showed that the content is not consistent among different pretreatment methods. However, the metalion content among these three methods are in the order of Fe > Mn > Cu, with the average recovery rate between 92.6% and 119.6%. The RSD is less than 2.86%. It was concluded that this method is with high accuracy and stability as well as reliable accurate re-sults. It also proved that Peach pulp . is rich in Fe, Cu and Mn. It provides some useful information for further pharmacological study of Peach pulp .

Preventive effects of sevoflurane treatment on lung inflammation in rats

OBJECTIVE@#To observe the effects of sevoflurane treatment on lung inflammation in rats with lipopoIysaccharide-induced acute lung injury (ALI).@*METHODS@#The rat model of ALI was established by intratracheal instillation of lipopolysaccharide (LPS). 45 infantile SD rats [body weight (272±15) g] were randomly divided into 3 groups (n=15): control group, LPS group, sevoflurane group. NS (1 mL/kg) was instillated in rats' airways of control group; LPS (5 mg/kg) was instillated in rats' airways of LPS group. Sevoflurane group rats received sevoflurane (2.4%) inhalation for a hour after LPS was instillated in rats' airways. Six hours after NS or LPS instillation, all rats were exsanguinated. Lung tissues were examined by HE staining. Expressions of TNF-α and ICAM1 mRNA were detected by semiquantitative RT-PCR techniques. The protein level of TNF-α and ICAM1 were assessed by western blot techniques.@*RESULTS@#In LPS group the permeability of lung tissues increased, organizational structure severely damaged and the alveolar wall tumed thick, with interstitial edema and Europhiles infiltrated increasingly. The LPS group had higher mRNA expressions of TNF-α and ICAM1 than control group and sevoflurane group (P<0.05), and LPS group had higher protein level of TNF-α and ICAM1 than control group and sevoflurane group (P<0.05).@*CONCLUSIONS@#Sevoflurane treatment can attenuate lung inflammation in rats with lipopolysaccharide-induced acute lung injury.

Relationship between HPV-DNA status and p16 protein expression in oropharyngeal squamous cell carcinoma and their clinical significance / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the relationship between HPV-DNA status and p16 protein expression in oropharyngeal squamous cell carcinoma (OSCC) and their clinical significance.</p><p><b>METHODS</b>Sixty-six patients with oropharyngeal squamous cell carcinomas treated in the Cancer Hospital of Chinese Academy of Medical Sciences from Jan. 1999 to Dec. 2009 were included in this study. Their formalin-fixed and paraffin-embedded tumor tissue blocks met the eligibility criteria and were used in this study. A "sandwich" technique was used to prepare paraffin sections for HPV-DNA analysis. HPV-DNA was detected using the SPF10 LiPA25 version 1 assay. The expression of p16 protein was detected by immunohistochemistry. The survival rates of patients with different HPV-DNA and p16 protein status were analyzed.</p><p><b>RESULTS</b>HPV-DNA was detected in 11 (16.7%) of all specimens. Expression of p16 protein was detected in 9 of the 11 patients with HPV-positive tumors, and in 12 patients of 55 HPV-negative tumors. The expression of p16 protein was highly correlated with the presence of HPV-DNA (P < 0.001). The tumors were classified into three groups based on the p16 protein expression and HPV-DNA status: group A (9 patients): HPV(+) and p16 protein(+); group B (14 patients): HPV-DNA(+)/p16 protein(-) or HPV-DNA(-)/p16 protein(+); and group C (43 patients): HPV-DNA(-)/p16 protein(-). The 3-year OS rates of these 3 groups were 100%, 77.8% and 42.0% (P = 0.001), and their DSS rates were 100%, 77.8% and 46.4%, respectively(P = 0.004).</p><p><b>CONCLUSIONS</b>In oropharyngeal squamous cell carcinomas, p16 protein expression is highly correlated with the presence of HPV-DNA, and might be a surrogate marker for HPV-positive OSCC. Combination of p16 protein and HPV-DNA status detection may help to more accurately stratify oropharyngeal carcinomas and predict their prognosis.</p>

Analysis of risk factors for anastomotic infectious complications following bowel resection for Crohn disease / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the risk factors for anastomotic infectious complications after bowel resection in patients with Crohn disease.</p><p><b>METHODS</b>Clinical data of 124 patients with Crohn disease undergoing bowel resection between January 1990 and October 2012 were analyzed retrospectively. The risk factors were identified by χ(2) test and Logistic regression.</p><p><b>RESULTS</b>Fourteen patients (12.3%, 14/114) developed anastomotic infectious complications in the postoperative period, including anastomotic leak (n=7), intra-abdominal abscess (n=6), and enterocutaneous fistula (n=1). Crohn disease activity index (CDAI)>150 (OR=2.185, 95%CI:1.098-6.256, P=0.040), steroid usage (OR=2.674, 95%CI:1.118-8.786, P=0.027), and the presence of preoperative abscess/fistula (OR=3.447, 95%CI:1.254-10.462, P=0.014) were identified as independent risk factors of anastomotic infectious complications. In the absence of these 3 risk factors, the rate of anastomotic infectious complication was 5.7% (3/53), which increased to 11.4% (4/35) when one risk factor was present, 21.1% (4/19) when two risk factors were present, and 42.9% (3/7) when all the 3 risk factors were present.</p><p><b>CONCLUSIONS</b>CDAI>150, steroid usage and preoperative abscess/fistula are associated with higher rates of anastomotic infectious complications following bowel resection for Crohn disease. A prudent management should be carried out if risk factors can not be eliminated preoperatively.</p>

Human papillomavirus infection in oropharyngeal squamous cell carcinoma and prognosis: a preliminary analysis of 66 cases / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To analyze the relationship between the prognosis of patients with oropharyngeal squamous cell carcinoma (OSCC) and human papillomavirus (HPV) infection in OSCC.</p><p><b>METHODS</b>Sixty-six patients with oropharyngeal carcinoma who met the enrollment criteria during the period from January 1999 to December 2009 were retrospectively reviewed. The presence or absence of HPV oncogenic types in OSCC specimen was determined by multiplex polymerase chain reaction (PCR). Overall survival (OS) and disease specific survival (DSS) for HPV-positive and HPV-negative patients were estimated by Kaplan-Meier analysis. Cox regression model was used for multivariate analysis.</p><p><b>RESULTS</b>HPV-DNA was detected in 11(16.7%) of all specimens. Among them, 7 were positive for HPV-16, 1 for HPV-16/11, 1 for HPV-35, 1 for HPV-58/52, and 1 for HPV-33/52/54. With the follow-up of 3-78 months (a median of 24.5 months), patients with HPV-positive tumors had significantly better overall survival (χ2=5.792, P=0.016) and disease specific survival (χ2=4.721, P=0.030), the 3-year OS and DSS were 90.0% vs 52.4% and 90.0% vs 56.4%, respectively. Multivariate analysis by Cox regression model showed that HPV infection and nodal status were both independent prognostic factors for patients with OSCC (P<0.05).</p><p><b>CONCLUSIONS</b>Patients with HPV-positive OSCC have significantly better prognosis than patients with HPV-negative tumors. HPV infection is an independent prognostic factor.</p>

R-CHOP regimen can significantly decrease the risk of disease relapse and progression in patients with non-germinal center B-cell subtype diffuse large B-cell lymphoma / 癌症

To further explore the role of rituximab when added to the CHOP-like regimen in the treatment of immunohistochemically defined non-germinal center B-cell subtype (non-GCB) diffuse large B-cell lymphoma(DLBCL), 159 newly diagnosed DLBCL patients were studied retrospectively based on the immunohistochemical evaluation of CD10, Bcl-6, MUM-1, and Bcl-2. Altogether, 110 patients underwent the CHOP-like regimen, and rituximab was added for the other 49 patients. Cox regression analysis showed that compared with the CHOP-like regimen, the rituximab-based regimen(R-CHOP regimen) significantly decreased the risk of disease relapse and progression in CD10-negative patients (P=0.001), Bcl-6-negative patients (P=0.01), and MUM-1-positive patients (P=0.003). The risk of disease relapse in patients with non-GCB subtype (P=0.002) also decreased. In contrast, patients with the opposite immunohistochemical marker expression profile and GCB subtype did not benefit from treatment with the R-CHOP regimen. In addition, non-GCB subtype patients had a significantly higher expression rate of Bcl-2 than GCB subtype patients (P=0.042). Although univariate analysis found that both Bcl-2-positive and -negative patients had significantly higher event-free survival rates with the R-CHOP regimen, only Bcl-2 positivity (P=0.004) maintained significance in the Cox regression analysis. We conclude that the addition of rituximab can significantly improve the prognosis of patients with non-GCB subtype DLBCL, which is closely related to the expression of CD10, Bcl-6, MUM-1, and Bcl-2.

Efficacy of peripheral blood stem cell transplantation versus conventional chemotherapy on anaplastic large-cell lymphoma:a retrospective study of 64 patients from a single center / 癌症

Anaplastic large-cell lymphoma (ALCL) is characterized by frequently presenting adverse factors at diagnosis. Many groups believed aggressive treatment strategies such as autologous stem cell transplantation brought survival benefit for ALCL patients. However, few compared these approaches with conventional chemotherapy to validate their superiority. Here, we report a study comparing the efficacy of peripheral blood stem cell transplantation (PBSCT) and conventional chemotherapy on ALCL. A total of 64 patients with primary systemic ALCL were studied retrospectively. The median follow-up period was 51 months (range, 1-167 months). For 48 patients undergoing conventional chemotherapy only, the 4-year event-free survival (EFS) and overall survival (OS) rates were 70.7% and 88.3%, respectively. Altogether, 16 patients underwent PBSCT, including 11 at first remission (CR1/PR1), 3 at second remission, and 2 with disease progression during first-line chemotherapy. The 4-year EFS and OS rates for patients underwent PBSCT at first remission were 81.8% and 90.9%, respectively. Compared with conventional chemotherapy, PBSCT did not show superiority either in EFS (P = 0.240) or in OS (P = 0.580) when applied at first remission. Univariate analysis showed that patients with B symptoms (P = 0.001), stage III/IV disease (P = 0.008), bulky disease (P = 0.075), negative anaplastic lymphoma kinase (ALK) expression (P = 0.059), and age ≤ 60 years (P = 0.054) had lower EFS. Furthermore, PBSCT significantly improved EFS in patients with B symptoms (100% vs. 50.8%, P = 0.027) or bulky disease (100% vs. 52.8%, P = 0.045) when applied as an up-front strategy. Based on these results, we conclude that, for patients with specific adverse factors such as B symptoms and bulky disease, PBSCT was superior to conventional chemotherapy in terms of EFS.

Detection of human papillomavirus in oropharyngeal squamous cell carcinoma / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the infection rate and subtypes of human papilloma virus(HPV) in patients with oropharyngeal squamous cell carcinoma (OSCC) and analyze the clinicopathologic features of patients with or without HPV infection.</p><p><b>METHODS</b>A total of 66 biopsy or surgical specimens of OSCC archived in the Pathology Department of Chinese Academy of Medical Sciences were analyzed by polymerase chain reaction (PCR), and the generic amplification products were detected by DNA enzyme immunoassay (DEIA) and typed by reverse hybridization line probe assay.</p><p><b>RESULTS</b>HPV-DNA was detected in 11 (16.7%) of all specimens. Among them, 7 were infected with HPV-16,and the remaining 4 patients were infected with HPV-16/11, HPV-35, HPV-58/52, and HPV-33/52/54, respectively. HPV-16 was detected in 72.7% of all positive specimens. There were more females in HPV-positive group than HPV-negative group (36.4% vs. 1.8%,P=0.002). Patients with HPV-positive tumors were more likely to be non-smokers (36.4% vs. 0,p=0.001) and non-drinkers (45.5% vs. 1.8%,p=0.001) than those with HPV-negative tumors. The proportion of moderately or poorly differentiated tumors was higher in HPV-positive patients than HPV-negative patients (81.8% vs. 63.7%), although without statistical significance (p=0.409). No difference was observed in T classification, N classification, and overall tumor stage.</p><p><b>CONCLUSIONS</b>HPV infection rate was 16.7% in this cohort. HPV-positive OSCC has its unique etiologic and clinicopathological characteristics.</p>

Primary superficial small cell neuroendocrine carcinoma of esophagus: clinicopathologic and immunohistochemical analysis of 15 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic and immunohistochemical features of primary superficial esophageal small cell neuroendocrine carcinoma (ESCNC).</p><p><b>METHODS</b>The clinical, pathologic and immunohistochemical features were retrospectively analyzed in 15 cases of superficial ESCNC. An immunohistochemical study for chromogranin A, neuron-specific enolase, synaptophysin, CD56, TTF-1, 34βE12, AE1/AE3, and CK10/13 was performed.</p><p><b>RESULTS</b>Superficial ESCNC accounted for 4.8%(15/312) of all cases of superficial carcinoma of the esophagus encountered during the same period. The median survival time was 19 months and the mean survival time was 23.7 months after diagnosis. The one, two and five-year survival rates were 10/15, 5/15 and 1/15, respectively. The immunophenotypic profile was as follows: neuron-specific enolase (15/15), synaptophysin (15/15), AE1/AE3 (15/15), CD56 (14/15), TTF-1 (9/15), chromogranin A (8/15), 34βE12 (1/15) and CK10/13 (0/15).</p><p><b>CONCLUSIONS</b>Superficial ESCNC is a rare and aggressive malignant tumor with poor prognosis. Surgical resection coupled with post-operative chemoradiotherapy is the mainstay of treatment. The immunohistochemical study is valuable in pathologic diagnosis and differential diagnosis.</p>

Comparison of histopathologic changes and expression of biomarkers in breast carcinoma before and after neoadjuvant chemotherapy / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between the pathologic responses and histologic type, grade, the expression of ER, PR and HER2 and their changes in breast carcinoma before and after neoadjuvant chemotherapy (NAC).</p><p><b>METHODS</b>Two-hundred and nine cases of breast cancer with NAC were analyzed and clinical, pathologic data were evaluated based on the Miller and Payne ( MP) grading system. The expression of ER, PR and HER2 in the cancers before and after NAC were detected by immunohistochemistry (MaxVision method). SPSS 15.0 software was used to conduct statistical analysis.</p><p><b>RESULTS</b>(1) Pathologic responses to the NAC were graded as MP1 (14 cases), MP2 (35 cases), MP3 (106 cases), MP4 (36 cases) and MP5 (18 cases); (2) The expression of ER in core needle biopsy had related negatively to the pathologic response (chi2 = 33.083, P = 0.001). However, the histologic type, grade, ER and PR status, and HER2 expression in surgically-removed specimens had not related to the pathologic response (P>0.05); (3) After NAC, the pathologic type and grade changed in 6. 8% (9/132) and 34.9% (30/86) of the cases, and the rates of changes in the expression of ER, PR and HER2 were 42.4% (75/177), 55.4% (98/177) and 26.6% (46/173) , respectively. Only the expression of HER2 had significant difference between before and after neoadjuvant chemotherapy (P = 0.049). The changes in other data had no relationship with the pathologic response (P>0.05).</p><p><b>CONCLUSIONS</b>Analysis of core needle biopsy can provide important information to predict the pathologic responses to the NAC. The pathologic appearance, grade, ER, PR and HER2 in breast carcinoma may change after NAC. It is necessary to examine the histologic type, grade and the expression of ER, PR and HER2 after NAC once more.</p>

Expressions of the γ2 chain of laminin-5 and secreted protein acidic and rich in cysteine in esophageal squamous cell carcinoma and their relation to prognosis / 癌症

Previous studies have shown that the expressions of the γ2 chain of laminin-5 and secreted protein acidic and rich in cysteine (SPARC) play important roles in oncogenesis and the development of carcinoma. To assess the expressions of laminin-5 γ2 chain and SPARC in esophageal squamous cell carcinoma (SCC), and to clarify the prognostic significance of the expressions of laminin-5 γ2 chain and SPARC in esophageal SCC, we detected the expressions of laminin-5 γ2 chain and SPARC in cancer tissue and corresponding normal mucosa from 116 patients with advanced (stages II-IV) esophageal SCC using the tissue microarray-based immunohistochemistry and analyzed the correlation of the expressions with clinicopathologic characteristics and survival. We found that in normal esophageal tissues, laminin-5 γ2 chain was expressed in the basement membrane, whereas in esophageal SCC tissues, laminin-5 γ2 chain was expressed in the cytoplasm of carcinoma cells, with a positive rate of 72.4%. SPARC was not detected in normal esophageal mucosa, but was expressed in stromal fibroblasts in 84.6% of esophageal SCC cases and in cancer cells in 7.8% of esophageal SCC cases. There was a significant correlation between laminin-5 γ2 chain and stromal SPARC expression in esophageal SCC (Spearman's rho=0.423, P<0.001). The expressions of both laminin-5 γ2 chain and stromal SPARC were correlated with survival (P=0.032 and P=0.034, respectively). In stage-II esophageal SCC, the expression of laminin-5 γ2 chain was significantly correlated with survival (P=0.023), while the expression of SPARC was not significantly correlated with survival (P=0.154). Patients with elevated levels of laminin-5 γ2 chain and SPARC expressions had a poorer prognosis than did those lacking elevated levels of laminin-5 γ2 chain expression and/or elevated levels of SPARC expression (P=0.001). In stage-II esophageal SCC, patients with elevated levels of laminin-5 γ2 chain and SPARC expressions had a poorer prognosis (P<0.001). These results suggest that laminin-5 γ2 chain and SPARC may play roles in the progression of esophageal SCC and their simultaneous expression is correlated with poorer prognosis, especially in patients with stage-II SCC.

DNA microarrays-based microRNA expression profiles derived from formalin-fixed paraffin-embedded tissue blocks of squammous cell carcinoma of larynx / 中华病理学杂志

<p><b>OBJECTIVE</b>To establish DNA microarrays-based microRNA (miRNA) expression profiles of squamous cell carcinoma of larynx, using archived formalin-fixed paraffin-embedded tissue blocks, and to screen out and identify the differentially expressed miRNAs associated with the biological characteristics of this malignant disease.</p><p><b>METHODS</b>Total RNA was prepared from the formalin-fixed paraffin-embedded tissue blocks. After quality identification and fluorescent labeling, the RNA samples were hybridized with the Agilent human miRNA microarrays which contains 723 probes for human miRNAs. The data was processed with the softwares GeneSpring GX and R-Project.</p><p><b>RESULTS</b>From the formalin-fixed paraffin-embedded tumor blocks collected, 24 RNA samples were obtained with the quality accorded to the requirement of miRNA microarray analysis, and both the hybridization and consequent data processing were accomplished. A total of 319 miRNAs were identified and among them 96 were detected in all the 24 formalin-fixed paraffin-embedded blocks of laryngeal carcinoma; and 5 differentially expressed miRNAs (false discovery rate < 0.05) were found to be associated significantly with the lymphatic metastasis of laryngeal squamous cell carcinoma (P < 0.05), including miR-23a(*), miR-28-5p, miR-15a, miR-16 and miR-425.</p><p><b>CONCLUSIONS</b>Histopathological archives of well-annotated formalin-fixed paraffin-embedded tissue specimens are the valuable resources for miRNA study including to collect RNA samples for miRNA microarray analysis. A panel of differentially expressed miRNAs (miR-23a(*), miR-28-5p, miR-15a, miR-16 and miR-425) derived from the miRNA expression profile may serve as the potential molecular biomarkers for the prediction of metastasis development in laryngeal squamous cell carcinoma.</p>

Expression of fascin and CK14 in different histological types of cancer and its differential diagnostic significance / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate and analyze the expression of fascin and CK14 in multiple histological types of cancer and to explore the potential value of the two proteins as markers in diagnosis and differential diagnosis of various cancer types.</p><p><b>METHODS</b>Tissue microarray containing esophageal squamous cell carcinoma (SCC), lung SCC, larynx SCC, uterine cervical SCC, SCC of external genital organs, lung adenocarcinoma, gastric adenocarcinoma, colorectal adenocarcinoma, heptocellular carcinoma, pancreatic ductal adenocarcinoma, breast infiltrating ductal carcinoma, thyroid papillary carcinoma, uterine endometrioid adenocarcinoma, ovarian serous adenocarcinoma and renal clear cell carcinoma, 30 cases each, as well as corresponding normal controls was constructed. The expression of fascin and CK14 among different types of carcinoma and corresponding normal controls was detected by immunohistochemistry.</p><p><b>RESULTS</b>In normal esophagus, bronchus, larynx, uterine cervix and skin, fascin was mainly expressed in the basal cells or reserve cells, but the expression was diffuse in esophageal SCC, lung SCC, larynx SCC, uterine cervical SCC and SCC of external genital organs, with a positive rate of 90.0%, 90.0%, 96.7%, 78.6% and 89.7%, respectively. In the normal tissue of other organs, except breast and uterine endometrium, fascin was negative. In lung adenocarcinoma, gastric adenocarcinoma, colorectal adenocarcinoma, hepatocellular carcinoma, pancreatic ductal adenocarcinoma, breast infiltrating dutal adenocarcinoma, thyroid papillary carcinoma, uterine endometrioid adenocarcinoma, ovarian serous adenocarcinoma and renal clear cell carcinoma, the positive rates were 38.0%, 23.3%, 14.3%, 10.3%, 73.3%, 13.3%, 6.7%, 60.0%, 66.7% and 10.0%, respectively. The difference between fascin expression in SCC and in other histological types was statistically significant (P < 0.001). CK14 was mainly expressed in the basal cells, reserve cells or myoepithelia of normal tissues. The positive rates of CK14 were 76.7%, 36.7%, 83.3%, 60.7% and 96.3% in esophageal SCC, lung SCC, larynx SCC, uterine cervical SCC and SCC of external genital organs, respectively. It was weak and focal in lung adenocarcinoma, gastric adenocarcinoma, colorectal adenocarcinoma, hepatocellular carcinoma, pancreatic ductal adenocarcinoma, breast infiltrating dutal adenocarcinoma, thyroid papillary carcinoma, uterine endometrioid adenocarcinoma, ovarian serous adenocarcinoma, and renal clear cell carcinoma, with a positive rate of 13.3%, 13.3%, 20.7%, 41.4%, 46.7%, 6.7%, 40.0%, 13.3%, 20.0% and 6.7%, respectively. The difference between CK14 expression in SCC and in other histological types was statistically significant (P < 0.001). The difference between co-expression of fascin/CK14 in SCC and in other histological types was also statistically significant (P < 0.001).</p><p><b>CONCLUSION</b>Fascin and CK14 are highly expressed in SCC, compared with other histological types of carcinoma. Combination of fascin and CK14 should be a valuable marker in diagnosis and differential diagnosis of carcinoma.</p>