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.

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>

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>

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.

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>

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.

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>

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>

Differences between clinical response and pathologic response of breast cancer after neoadjuvant chemotherapy / 中华病理学杂志

<p><b>OBJECTIVE</b>to investigate the pathologic basis of the difference between clinical response and pathologic response of breast carcinoma after neoadjuvant chemotherapy.</p><p><b>METHODS</b>two hundred and nine cases of breast cancer with neoadjuvant therapy were analyzed and clinical data were collected from June, 2005 to December, 2007. All patients had core needle biopsy taken before neoadjuvant chemotherapy and were operated within 4 weeks after neoadjuvant chemotherapy. Clinical examination, X-ray of breast and/or B ultrasonography of primary breast focus were taken before and after neoadjuvant chemotherapy. Clinical responses of breast primary focus were evaluated according to RECIST (response evaluation criteria in solid tumors) version 1.1.Pathologic responses of breast primary focus were evaluated according to Miller and Payne (MP) grading system. SPSS 15.0 software was used to statistical analysis.</p><p><b>RESULTS</b>(1) Clinical responses basing on clinical examination showed complete response, partial response, stable disease and progressive response, in 33, 124, 41 and 11 cases respectively. (2) Eighty-seven cases had X-ray of breast taken before and after neoadjuvant chemotherapy. Clinical response basing on X-ray, showed complete response, partial response and stable disease in 8, 42 and 37 cases respectively. (3) Pathologic responses of breast primary focus were as MP1 (14 cases), MP2 (35 cases), MP3 (106 cases), MP4 (36 cases) and MP5 (18 cases). (4) The clinical response basing on clinical examination were related to the pathologic response (χ(2) = 33.668, P = 0.001); and the clinical response basing on X-ray of breast were also related to the pathologic response (χ(2) = 22.404, P = 0.004). (5) The pathologic basis of the difference between the pathologic response and the clinical response basing on X-ray of breast were: embolism of carcinoma, mucinous carcinoma, intraductal carcinoma with ossifying-type calcification, nodular fibrosis and others.</p><p><b>CONCLUSIONS</b>the clinical response may be related to the pathologic response. The difference between the two may be caused by pathologic changes. Some benign and malignant pathologic changes may contribute to the under-estimation of clinical response over pathologic response; whereas embolism of carcinoma may contribute to the over-estimation of clinical response over pathologic response.</p>

Morphologic assessment of response to neoadjuvant chemotherapy in breast cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the histological criteria of breast cancer response to neoadjuvant therapy.</p><p><b>METHODS</b>One hundred and fifty-four cases of breast cancer receiving neoadjuvant therapy were collected from June, 2005 to June, 2007 and the clinical data were analyzed. All patients were operated on within 4 weeks after neoadjuvant therapy. All specimens were assessed by the standard method of Miller and Payne (MP) grading system. The response to neoadjuvant therapy were assessed by two pathologists independently, using MP grading system and common grading system separately.</p><p><b>RESULTS</b>The response rate using the MP grading system were grade 1 in 12 cases (7.8%), grade 2 in 33 cases (21.4%), grade 3 in 64 cases (41.6%), grade 4 in 31 cases (20.1%) and grade 5 in 14 cases (9.1%). Using the common grading system, the response were mild in 51 cases (33.1%), moderate in 71 cases (46.1%) and severe in 32 cases (20.8%). MP grading system may be related to common grading system (chi2 = 186.660, P < 0.01). Follow up information were available in 147 cases, with 14 cases showing recurrence, metastasis or death from the disease. The MP grading system may be related to the outcome (chi2 = 11.612, P = 0.020), but not the common grading system (chi2 = 0.881, P = 0.644).</p><p><b>CONCLUSION</b>MP grading system may be one of the prognostic factors in the neoadjuvant therapy of breast cancer.</p>

Diagnostic value of transbronchial needle aspiration combined with transesophageal endoscopic ultrasound-guided fine needle aspiration in mediastinal and pulmonary hilar lesions / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the value of transbronchial needle aspiration (TBNA) combined with transesophageal endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in the diagnosis of mediastinal and pulmonary hilar lesions as well as in the lymph node staging (N staging) of lung cancer.</p><p><b>METHODS</b>129 patients with mediastinal and pulmonary hilar lesions underwent either TBNA or EUS-FNA with cytological needle aspiration. The samples obtained from TBNA or EUS-FNA were examined by both cytologiy and histopathology.</p><p><b>RESULTS</b>Of the 129 patients, 59 underwent TBNA and 70 EUS-FNA. The diagnostic rate were 84.7% (50/59) by TBNA and 94.3% (66/70) by EUS-FNA, resepectively. The diagnosis of 116 (89.9%) patients were confirmed by either TBNA or EUS-FNA. The pathological and cytological diagnostic rates were 92.2% (107/116) and 88.0% (102/116), resepectively. The diagnostic rate was elevated by 8.4% (9/107) through pathological examination. The histological classification rates by cytological and pathological examination were 73.8% (76/116) and 89.3% (92/103), respectively. The diagnostic rate of histological classification was elevated by 35.5% (27/76) through pathological examination.</p><p><b>CONCLUSION</b>The combination of TBNA and EUS-FNA can improve the diagnostic rate for wider mediastinal and pulmlonary hilar lesions. Pathological examination of the samples obtained from the TBNA and EUS-FNA can elevate not only the rate of diagnosis but also the rate of histological classification.</p>

Characteristics of 3.0T dynamic contrast-enhanced magnetic resonance imaging of lung cancer and its correlation with microvessel density / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the characteristics of 3.0T dynamic contrast-enhanced magnetic resonance (DCE-MR) imaging of lung cancer and its correlation with microvessel density (MVD).</p><p><b>METHODS</b>Thirty-seven patients with pathologically proven lung cancer underwent DCE-MR with liver acquisition with volume acceleration sequence. DCE-MR images were acquired intermittently for a total of 4 minutes on a 3.0T MR scanner. The relative enhancing percentage (SI%) at each time point was measured. The shapes of T-SI% curves were defined as A (rapidly ascending followed by a descending branch) and B (rapidly ascending branch followed by a plateau). The early peak enhancement (SIEP%), early peak time (TEP), maximum enhancement (SIpeak%), and peak time (Tpeak) were recorded and compared according to different dimensions, locations, histological types, and differentiation grades of lung cancer. Tumour specimens were immunostained for CD31 and CD34 in ten patients who had undergone surgical resections. The enhancement values were correlated with MVD. Results The SIEP% and SIpeak% of tumors with smaller dimensions (< or = 5 cm) were significantly higher than those with larger dimensions (> 5 cm) (P = 0.014, P = 0.024). The SIEP% and SIpeak% were positively correlated with the tumor MVD. Conclusion The SIEP% and SIpeak% of lung cancer correlate with tumor dimension and can reflect MVD in tumor.</p>

Diagnostic value of core needle biopsy before neoadjuvant chemotherapy for breast cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>To assess the diagnostic value of core needle biopsy (CNB) before neoadjuvant chemotherapy for breast cancer.</p><p><b>METHODS</b>One hundred and nineteen breast cancer cases underwent neoadjuvant chemotherapy in our hospital during the period from June, 2005 to January, 2007 were analyzed. CNB was carried out before starting chemotherapy. The hematoxylin and eosin-stained slides of CNB taken before and after neoadjuvant chemotherapy were reviewed independently by two pathologists, and the rate of consistency was verified.</p><p><b>RESULTS</b>Amongst the 119 cases studied, 110 cases were confirmed to be carcinoma, including 105 cases of invasive carcinoma and 5 cases of ductal carcinoma-in-situ. The rate of consistency was 97.22% (105/108).</p><p><b>CONCLUSION</b>CNB has important value in distinguishing benign from malignant lesions, as well as in confirming the diagnosis of invasive carcinoma before starting neoadjuvant chemotherapy.</p>

Expression of annexin I in different histological types of carcinomas / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of annexin I in esophageal squamous cell carcinoma (SCC) and carcinomas of other histological types in order to analyze the correlation between the expression of annexin I and carcinogenesis.</p><p><b>METHODS</b>First, a set of tissue microarray was established, which consisted of SCC from the esophagus (208 cases), lung, larynx, cervix, and external genital organs; adenocarcinomas from the lung, stomach, colon and rectum, liver, pancreas, breast, thyroid and kidney with 30 cases in each group, meanwhile, the corresponding normal tissue was also obtained for control. Immunohistochemistry was used to detect the expression of annexin I in different types of carcinomas and the corresponding normal controls from different organs. The correlation between the expression of annexin I and the clinicopathological feature was analyzed and compared, which included age, gender, differentiation grade and lymph node metastasis.</p><p><b>RESULTS</b>It was found that the expression of annexin I was decreased in esophageal SCC, when compared with normal esophageal squamous epithelia (P < 0.001), the similarity was also found in SCC of the lung, larynx and cervix. However, though negative in normal epidermis, annexin I expression was detected in some cases with SCC from external genital organs. Annexin I was found to be overexpressed in adenocarcinomas of the lung, stomach, colon and rectum, liver, pancreas, breast, thyroid and kidney, particularly very strong expression of annexin I was seen in lung adenocarcinoma, uterine endometrioid adenocarcinoma and ovarian serous adenocarcinoma. Interestingly, it was found to be positive in all thyroid papillary carcinomas, but negative in all normal thyroid glands. However, annexin I expression was found to be negative in all hepatocellular carcinoma and normal hepatocytes; and it was only detected in myoepithelium of normal breast tissue, but not in ductal luminal cells, and rarely in infiltrating ductal adenocarcinoma. In SCC, annexin I expression was stronger in well differentiated ones than that in the poorly differentiated ones. However, contrasting with SCC, in the adenocarcinomas from different organs, annexin I expression was much stronger in poorly differentiated ones than that in the well differentiate ones, especially in the adenocarcinomas from stomach, colon and rectum, pancreas, ovarian and kidney.</p><p><b>CONCLUSION</b>Annexin I expression is quite different among different types of carcinomas, and is correlated with histopathological type and differentiation grade. Further study is needed to investigate its role in the carcinogenesis.</p>

Prognostic significance of micropapillary pattern in pulmonary adenocarcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluate the prognostic significance of micropapillary pattern (MPP) in adenocarcinoma of lung.</p><p><b>METHODS</b>Ninety-one consecutively excised cases of pulmonary adenocarcinoma, including follow-up data, were retrospectively studied. These tumors were divided into 2 major groups: those with MPP and those without MPP. The former was further subdivided according to extent of the micropapillary component, as follows: MPP + (constituting 1% to 10% of the tumor), MPP ++ (constituting 11% to 30% of the tumor) and MPP +++ (constituting more than 30% of the tumor).</p><p><b>RESULTS</b>The overall 5-year survival rate was 64.8%. The 5-year survival rates were 88.9% for stage I tumors, 46.2% for stage II tumors, and 23.8% for stage III tumor respectively (P = 0.000). The extent of micropapillary component showed no correlation with tumor stage, size and 5-year survival rate (P = 0.065, 0.358 and 0.206, respectively). On the other hand, the 5-year survival rate was 41.5% for patients in the MPP-positive group (number = 41) and 84.0% for patients in the MPP-negative group (number = 50). The percentage of nodal metastasis in MPP-positive group was also higher than that in MPP-negative group (P = 0.000). In pulmonary adenocarcinoma, this characteristic histology correlated with tumor stage and size, but not with patient's gender and smoking history. Within the same stage, the 5-year survival rates of MPP-positive and MPP-negative groups were as follows: for stage I, 78.6% versus 92.6% (P = 0.1548), for stage II, 30.0% versus 100% (P = 0.0598), and for stage III, 17.7% versus 28.6% (P = 0.4045).</p><p><b>CONCLUSIONS</b>MPP in primary pulmonary adenocarcinoma, even when only constituting a minor component, predicts an aggressive clinical behavior and is associated with poor prognosis. Although it may not be an independent prognostic factor, presence of this histologic pattern should alert clinicians for more active treatment and closer follow up.</p>

A clinicopathological analysis of gastric lymphoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To discuss the clinicopathological features and prognostic factors of gastric lymphoma.</p><p><b>METHODS</b>83 gastric lymphoma cases were analyzed retrospectively in accordance to the criteria of the new World Health Organization classification for neoplastic diseases of the hematopoietic and lymphoid tissues. The correlations between clinicopathological features, therapeutic measures and survival were discussed.</p><p><b>RESULTS</b>The age of patients ranged from 25 to 77, with a median of 52. The number of males were similar to that of females. There were no specific symptoms. The most common symptoms were stomach ache (60 cases, 72%) or discomfort. The duration of symptoms was often long and with a history of chronic gastric diseases (21 cases, 25%). 13 cases had multiple lesions in the gastrointestinal mucosa. 51 cases (61%) were accompanied by lymph node involvement. According to the new World Health Organization classification for neoplastic diseases of the hematopoietic and lymphoid tissues, 57 cases were extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT)-type (MALT lymphoma), 23 were diffuse large B cell lymphoma accompanying MALT lymphoma, 2 were diffuse large B cell lymphoma and 1 was follicular lymphoma. Of all the cases, 31 were stage I E, 38 stage II E, 8 stage III E and 6 stage IV by the Ann Arbor staging system (1972). The total 5-year and 10-year survival rates were 77.8% and 70.1% respectively, with the mean survival time of 146 months. The 5-year and 10-year survival rates of MALT lymphoma were 77.4% and 72.3%, the 5-year and 10-year survival rates of diffuse large B cell lymphoma accompanying MALT lymphoma were 81.8% and 68.2%, the 5-year survival rate of diffuse large B cell lymphoma was 50.0%.</p><p><b>CONCLUSIONS</b>There are no specific symptoms in gastric lymphoma patients. Extranodal marginal zone lymphoma of MALT-type is the main histopathological type of gastric lymphoma, often accompanied by multiple mucosa involvement and also often accompanied by a history of chronic gastric disease. The lesion is usually localized for a long time, with a very good prognosis. Survival rate has a significant correlation with lymph node involvement and clinical stage. No correlations were found between the survival rates with age, gender, B symptoms, invasive depth of the wall of stomach, the size and range of the tumors or different therapeutic measures.</p>

Somatic mutations of VHL gene and HIF-1alpha expression in primary renal clear cell carcinomas / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the significance of somatic mutations of VHL gene and hypoxia-inducible factor-1alpha (HIF-1alpha) expression in primary renal clear cell carcinoma (RCC).</p><p><b>METHODS</b>Mutation of VHL gene and HIF-1alpha expression were detected by means of PCR, denaturing high-performance liquid chromatography (DHPLC), direct sequencing and immunohistochemistry in 32 samples from primary renal clear cell carcinoma patients.</p><p><b>RESULTS</b>In 32 RCC samples, 17 samples (53.1%) had and 32 samples of adjacent nonmalignant renal tissue had not mutations of VHL gene expression. Twelve RCC samples (70.6%) which had mutations of VHL gene expressed HIF-1alpha, and it had significant difference to 4 RCC (26.7%) samples which didn't have mutations of VHL gene (P < 0.05).</p><p><b>CONCLUSION</b>Mutations of VHL gene may play a significant role in the tumorigenesis of RCC, and HIF-1alpha expression correlates with it.</p>

TTF-1 expression and its diagnostic application in lung carcinomas / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To detect the expression of thyroid transcription factor 1 (TTF-1) and study its application in the diagnosis of lung carcinomas.</p><p><b>METHODS</b>Of 134 specimens from lung lobectomy, 105 were primary lung carcinomas including 76 non-small cell carcinomas (NSCLCs), 28 small cell lung cancers (SCLCs) and 1 complex carcinoma (SCLC and SCC), and 29 were metastatic carcinomas. Expression of TTF-1 was detected by immunohistochemistry. The expression level of TTF-1 was graded as, +:6% to 25% of tumor cells positive, ++:26% to 50%, +++:51% to 75%, and ++++:> 76%.</p><p><b>RESULTS</b>The positive nuclear immunoreactivity of TTF-1 was identified in 23 of 28 SCLCs (82.1%), but none in squamous cell cancer (SCC) (P < 0.001). The positive expression rate of TTF-1 in lung adenocarcinomas (ACs) was 73.8% (31/42). There was no correlation between TTF-1 expression and ACs differentiation or ACs subtypes (P > 0.05). All but one (thyroid follicular carcinoma) metastatic ACs were TTF-1-positive. Mesenchymal component and lymphoid or inflammatory cells were consistently TTF-1-negative.</p><p><b>CONCLUSION</b>A significant difference of TTF-1 expression may assist in distinguishing SCLC from SCC, lymphoma or inflammatory lesions. Owing to its restrictive expression in lung tissue, TTF-1 might be used to differentiate primary from metastatic adenocarcinoma of the lung.</p>