Resistance to apoptosis should not be taken as a hallmark of cancer / 癌症

In the research community, resistance to apoptosis is often considered a hallmark of cancer. However, pathologists who diagnose cancer via microscope often see the opposite. Indeed, increased apoptosis and mitosis are usually observed simultaneously in cancerous lesions. Studies have shown that increased apoptosis is associated with cancer aggressiveness and poor clinical outcome. Furthermore, overexpression of Bcl-2, an antiapoptotic protein, is linked with better survival of cancer patients. Conversely, Bax, CD95, Caspase-3, and other apoptosis-inducing proteins have been found to promote carcinogenesis. This notion of the role of apoptosis in cancer is not new; cancer cells were found to be short-lived 88 years ago. Given these observations, resistance to apoptosis should not be considered a hallmark of cancer.

Detection of micrometastases in sentinel lymph nodes of breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate an optimal examination method to detect micrometastases in sentinel lymph nodes (SLNs) of breast cancer.</p><p><b>METHODS</b>Firstly, the SLNs of breast cancer were found by 99mTc-DX isotope method. Secondly, all the SLNs which were negative by routine HE examination were serially sectioned at a 100 microm interval and stained by both HE and immunohistochemistry for detecting micrometastases. All tumor tissue paraffin blocks were also sectioned and stained with HE and immunohistochemistry as control.</p><p><b>RESULTS</b>Totally, 121 SLNs and 44 tumors of 59 patients were examined. Micrometastasis was found to be positive in 17 SLNs (14.0%) of 14 patients (23.7%). When examined number of sections was increased from one to three, more positive micrometastatic SLNs were detected by HE staining only (3, 7, 10 for 1, 2, 3 sections, respectively). When HE staining was combined with immunohistochemical staining for AE1/3 or CK19 or muc1, much more positive micrometastatic SLNs were found (14, 12, 16 for 1, 2, 3 sections, respectively). The more sections were examined, the more micrometastases in SLNs were found. Furthermore, micrometastasis was also found to be positively correlated with the tumor size and the expression of c-erbB2, MMP-2, VEGF. The larger the tumor size was or the stronger expression of the above mentioned biomarkers, the more micrometastases in SLNs could be found.</p><p><b>CONCLUSION</b>Serially sections at a 100 microm interval and staining with both HE and immunohistochemical technique using muc1 antibody may be the best way to detect micrometastases in sentinel lymph nodes in breast cancer patients.</p>

Intra-abdomen extragastrointestinal stromal tumors: a clinicopathologic study on 30 cases / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological characteristics and prognostic factors in patients with intra-abdomen extragastrointestinal stromal tumors (EGISTs).</p><p><b>METHODS</b>The data of 47 patients of mesenchymal neoplasms that arose from the abdominal cavity and retroperitoneum, collected from July 1987 to June 2003 in our hospital with complete clinical and pathological data, were investigated retrospectively. EGISTs were diagnosed by reviewing the tumor slides stained with hematoxylin and eosin (H&E). Immunohistochemistry staining were performed on CD117, CD34, smooth muscle actin, Desmin and S-100 proteins. The relations of various clinicopathologic characteristics and outcomes were examined.</p><p><b>RESULTS</b>Among the 47 cases, 30 tumors were confirmed to be EGISTs. Twelve cases arose from the mesentery, six from small omentum, eight from retroperitoneum and four from the abdominal cavity. The size of tumors ranged from 4 to 30 cm (median 12.5 cm) in diameter and the tumor cell components mainly included spindle cells (23 cases), epithelioid cells (4 cases), and mixed cells (3 cases). The follow-up rate was 90% and the median follow up time was 44 months. The patient survival rates at 1, 5 and 10 years were 79.7%, 59.5% and 45.4% respectively. Univariate analysis showed that tumor size >10 cm, tumor necrosis, mitoses > or =5/50HPF, obvious nuclear atypia, moderate and poor differentiated tumor cells were predictors of poor prognosis.</p><p><b>CONCLUSIONS</b>EGISTs have specific clinical behaviors. The parameters used for predicting GISTs prognosis are not completely applicable for EGISTs. Tumor necrosis, obvious nuclear atypia and mitoses > or =5/50HPF help to predict aggressive behaviors in EGISTs.</p>

Treatment option and outcome for patients with primary non-Hodgkin's lymphoma of the nasal cavity / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The optimal treatment for primary non-Hodgkin's lymphoma (NHL) of the nasal cavity remains controversial. This study was to analyze the initial response rate of radiotherapy and chemotherapy, and the influence of different treatment modalities on prognosis.</p><p><b>METHODS</b>From January 1996 to December 2002, the clinical data of 129 patients with previously untreated nasal NHL were retrospectively reviewed with all lesions confirmed by pathology. 116 patients were morphologically diagnosed as having nasal NK/T cell lymphoma. The immunophenotype was available in 57 cases and 52 (91.2%) of them were confirmed as NK/T-cell lymphoma. According to the Ann Arbor Staging System, 102 patients had stage I(E), 22 stage II(E), and 5 stage IV(E) disease. Among the 124 patients with stage I(E) and II(E) diseases, 22 patients received radiotherapy alone, 7 chemotherapy alone, and 95 combined modality therapy (CMT). Of these 95 patients treated with CMT, 45 patients were treated with radiotherapy followed by chemotherapy, and 50 with chemotherapy followed by radiotherapy. The primary treatment for stage IV(E) patients was chemotherapy with or without radiotherapy to the primary tumor.</p><p><b>RESULTS</b>The overall 5-year survival (OS) and disease free survival (DFS) for all patients was 68.0% and 55.8%, respectively. It was 71.7% and 60.9% for stage I(E), and 70.6% and 47.0% for stage II(E), respectively (P > 0.05). The OS and DFS at the 5th year were 83.1% and 68.0% for patients who achieved complete response (CR), and 18.0% and 15.5% for those who did not, respectively (P = 0.000). Of the 124 patients with stage I(E) and II(E) disease, 67 patients were treated with radiotherapy alone (22 patients) or radiotherapy followed by chemotherapy (45), whereas 57 were treated with chemotherapy followed by radiotherapy (50) or chemotherapy alone (7). The CR rate after radiotherapy was 74.7%, however, it was only 19.3% after chemotherapy (P = 0.000). Of the 46 patients with PR, SD or PD after chemotherapy, 42 still had locoreginally localized lesion and 31 of these patients achieved CR by following radiotherapy which revealed satisfactory results. For stage I(E) and II(E) disease, the 5-year OS and DFS were 76.0% and 65.0% for radiotherapy with or without chemotherapy, and 74.4% and 56.2% for chemotherapy followed by radiotherapy. The difference was statistically not significant. However, 7 stage I(E) and II(E) patients were treated with chemotherapy alone, and 4 of them died of disease progression, with 1-year survival of 26.7%.</p><p><b>CONCLUSION</b>The majority of Chinese patients with primary nasal NHL are NK/T cell in origin. The complete response rate by radiotherapy is much higher than that by chemotherapy. The addition of chemotherapy to radiotherapy did not improve the survival of patients with early stage nasal lymphoma. Radiotherapy is suggested as the primary treatment for stage I(E) and II(E) nasal NK/T cell lymphoma.</p>

Mediastinal lymph nodes micro-metastases in patients with clinical stage I-II lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate micro-metastasis in mediastinal lymph nodes (mLN) of patients with clinical stage I approximately II lung cancer and its clinical significance.</p><p><b>METHODS</b>A total of 181 mLN from 32 lung cancer patients in clinical stage I approximately II were collected during operation and their frozen sections at two different levels were examined immunohistochemically (IHC) with an anti-epithelial cell monoclonal antibody Ber-Ep4. Routine HE staining was done for comparison. The results were processed by Chi-square tests in SPSS 10.0 soft ware.</p><p><b>RESULTS</b>Fifteen of the 32 patients (46.9%) were found to have micro-metastasis in 21 of 181 mLN (11.6%) examined by immunohistochemical staining though routine histopathological examinations were negative. Of those 15 cases, micro-metastasis was detected in 9 only by IHC and in 6 both by IHC and HE stainings. The positive rate of micro-metastasis in N0, N1, and N2 stratified by routine pathology was 36.8% (7/19), 33.3% (2/6) and 85.7% (6/7), respectively (N0 vs N2, P < 0.05). When stratified according to clinical staging (cTNM), pathological staging (pTNM) and pathological staging on the basis of IHC (iTNM), the frequencies of N2 cases were 0, 18.8% and 46.9%, respectively (differences among the three groups: P < 0.01). Nine cases reported as N0(7) and N1(2) by routine histopathological examination were found to have micro-metastasis in mLN by IHC staining, therefore they were actually N2 cases.</p><p><b>CONCLUSION</b>IHC staining with a monoclonal antibody specific for epithelial cells (Ber-Ep4) is more sensitive in the detection of mediastinal micro-metastais than routine HE staining. Underestimation of the extent of mLN metastasis by cTNM and/or pTNM stagings frequently exists in patients with clinically early lung cancer.</p>

Differential diagnostic value of B72.3, Ber-EP4 and calretinin in serous effusions / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To determine the diagnostic value of B72.3, BerEP4 and calretinin in differentiating metastatic carcinoma cells from reactive mesothelial cells (RMC) in serous effusions by using immunocytochemical method (ICC), and to investigate the feasibility of ThinPrep (TP) preparation for ICC.</p><p><b>METHODS</b>One hundred fifty eight serous effusion specimens were examined by ICC on cell block (CB) sections (CB-ICC) using antibodies against of B72.3, BerEP4 and calretinin. Fourty-nine of the samples, ICC on ThinPrep slides (TP-ICC) and CB-ICC were performed concurrently.</p><p><b>RESULTS</b>The sensitivities of B72.3 and Ber-EP4 for detecting carcimoma cells were 76.9% and 69.2% respectively, and when combined the sensitivity was increased to 89.7%. The sensitivity and specificity of Calretinin for detecting mesothelial cells were 90.9% and 87.2% respectively. The sensitivity of B72.3 in differentiating cancer cells from reactive mesothelial cells by CB-ICC and TP-ICC was 78.9% and 68.4%. It was 78.9% and 68.4% of BerEP4 respectively. No statistical significance was observed between CB-ICC and TP-ICC in differentiating metastatic carcinoma cells from reactive mesothelial cells.</p><p><b>CONCLUSION</b>The combination of antibodies of B72.3, Ber-EP4 and calretinin is quite helpful as an auxiliary in differentiating metastatic carcinoma cells from reactive mesothelial cells. ThinPrep preparation slides may effectively replace the cell block sections for ICC in differential diagnosis of serous effusions.</p>

Multivariate analysis of prognosis in gastrointestinal stromal tumor / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To identify prognostic factors in patients with gastrointestinal stromal tumors (GIST).</p><p><b>METHODS</b>Hematoxylin and eosin (H&E) stained histopathological slides of tumors from patients with mesenchymal neoplasms growing in the gastrointestinal tract and abdomen were reviewed. Two histologically representative areas were identified and chosen for tissue microarray. Immunohistochemical staining was performed to demonstrate c-kit protein (CD117), CD34, smooth muscle actin, desmin and S-100 protein. The relations of various clinicopathologic features to outcome were analyzed.</p><p><b>RESULTS</b>The overall disease-specific survival of 194 patients was 93.5% at 1 year, 72.1% at 3 years and 63.2% at 5 years. Univariate analysis indicated that the tumor size, mitotic count, primary location, necrosis, high cellularity, mucosal invasion, mixed cell type, hemorrhage, direct tumor invasion of surrounding tissue, male sex, incompleteness of resection, cytologic atypia were significant predictors of survival. Multivariate analysis showed that tumor size, mitotic count, necrosis, direct tumor invasion of surrounding tissue and male sex were poor prognostic signs.</p><p><b>CONCLUSION</b>Tumor size and mitotic count are important prognostic factors. However, to evaluate the prognosis of these tumors, a surgical pathologist should incorporate multiple parameters into their histologic evaluation in attempt to reach an appropriate opinion on the aggressiveness of GIST.</p>

Analysis of prognostic factors in gastrointestinal stromal tumors of the small intestine / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the prognostic factors in patients with gastrointestinal stromal tumors of the small intestine.</p><p><b>METHODS</b>Tumor slides stained with hematoxylin and eosin from these patients were reviewed. Two histomorphologically representative areas were identified and arrayed on a tissue microarray. Immunohistochemistry staining were performed using antibodies to detect the expression of c-kit protein (CD117), CD34, smooth muscle actin, desmin, S-100, Ki-67, P53 and bcl-2 protein. The relationship between clinicopathologic features and prognosis was analyzed by univariate analysis.</p><p><b>RESULTS</b>The 1-, 3-, 5-year survival rate of 58 such patients were 98.3%, 69.7%, and 50.9% respectively. The prognosis was related with tumor size and gender by univariate analysis (P< 0.05).</p><p><b>CONCLUSION</b>More attention should be paid to the male patients with small intestine stromal tumors,especially those with tumors size> 5 cm, because those tumors are more likely to metastasize than smaller tumors (< or = 5 cm).</p>

A comparison of Thinprep and conventional smears / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze ThinPrep (TP) application by comparing TP slides with conventional smear (CS) slides in fine needle aspiration cytology.</p><p><b>METHODS</b>A total of 522 samples from the breast, metastatic cancer, lymph node, thyroid and salivary gland were used in parallel preparations of one TP slide and one CS slide. The paired slides were compared according to cell quality, overall cellularity, cell preservation, nuclear architecture and background.</p><p><b>RESULTS</b>Cell quality of TP was superior to CS in the breast group (36.2%, 28.0%, P > 0.05) and metastatic cancer group (51.0%, 14.9%, P < 0.05), but inferior to CS in lymph node group (16.5%, 58.2%, P > 0.05). Cellularities of TP and CS were similar in breast groups (25.1%), while TP had greater cellularity than CS in metastatic cancer group (32.2%, 21.8%, P > 0.05). Cell preservation and abnormal architecture of TP were superior to CS in breast group (36.7%, 12.1%, P < 0.05) and metastasis cancer group (60.9%, 9.4%, P < 0.05). Cell quality of TP slide was inferior to CS in lymph node group (16.5%, 58.2%, P < 0.05) with 27 of the 46 cases showing tuberculosis. Cell quality of TP and CS slide was similar in the thyroid and salivary gland group (35.3%). Myoepithelial cells of fibroadenoma on the TP slide were decreased in number and, due to the increased papillary and flattened cells, it was easy to diagnose benign lesion.</p><p><b>CONCLUSION</b>In the breast group and metastatic cancer group, cell quality of the TP slides is superior to CS, but they are similar in thyroid and salivary gland group. The difference of diagnosis criteria between TP and CS slides exists only in tuberculosis, partly the reactive hyperplasia cases.</p>

Relationship between overexpression of the RIalpha subunit of the cAMP-dependent protein kinase and clinicopathological features of lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the relationship between the overexpression of PKA RIalpha mRNA and cliniopathological parameters in lung cancer.</p><p><b>METHODS</b>RT-PCR was used to detect the expression of PKA RIalpha mRNA in 54 cases with human lung cancer and matched normal tissues.</p><p><b>RESULTS</b>(1) The expression of PKA RIalpha mRNA was significantly higher in cancer tissue (66.7%) than in normal tissues (20.4%) (P < 0.01). (2) The expression was significantly correlated with TNM stage (P < 0.01), being increased with TNM stage. (3) The expression was significantly higher in patients with positive lymph nodes than in those with negative lymph nodes (P < 0.01). (4) There were no significant associations of PKA RIalpha mRNA expression with histological type, differentiation grade or size of the tumor.</p><p><b>CONCLUSION</b>This study indicates that the overexpression of PKA RIalpha mRNA may play an important role in the progression, metastasis and prognosis of lung cancer.</p>

Expression of annexin II in human esophageal squamous cell carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the expression of annexin II in human esophageal squamous cell carcinoma (ESCC) and its relation with clinicopathological data.</p><p><b>METHODS</b>The expression of annexin II mRNA and protein in paired cancer tissues and their adjacent quasi-normal tissues were detected by RT-PCR, immunohistochemical method and densitometric scanning. The relation between annexin II expression and the status of tumor differentiation was analyzed.</p><p><b>RESULTS</b>The expression of annexin II was significantly lower in the tumor tissue than that in its paired normal counterpart both in mRNA and protein level (P < 0.05, P < 0.01). The protein expression of annexin II was significantly lower in moderately and poorly differentiated tumors than those in well differentiated ones (P < 0.05).</p><p><b>CONCLUSION</b>Down-regulation of annexin II in esophageal carcinogenesis may play an important role in squamous cell differentiation.</p>

Primary gastric endocrine tumors / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathological features of gastric neuroendocrine tumors.</p><p><b>METHODS</b>Twenty cases were reviewed. The specimens were formalin-fixed, paraffin-embedded and immunostained by S-P method.</p><p><b>RESULTS</b>Among the twenty cases, one case was carcinoid, three were malignant carcinoids, six had small cell carcinomas and ten had mixed extocrine--endocrine carcinomas. Immunohistological examination of tumor cells found 80% positive for S-100, NSE (85%), CgA (50%), SY (50%), gastrin (30%), serotonin (65%), AE1/AE3 (50%), and CEA (80%).</p><p><b>CONCLUSIONS</b>In the WHO classification, there are five histological types in endocrine tumors of gastrointestinal tract. They are carcinoid, malignant carcinoid, small cell carcinoma, mixed exocrine--endocrine carcinoma and tumor-like lesions. But some cases in our paper were so different that they could not be classified. The gastric endocrine tumors are different from intestinal endocrine tumors and in classification, treatment and prognosis.</p>

Induction of human oral carcinoma by human papillomavirus 16 E6/E7 and TPA / 中华实验和临床病毒学杂志

<p><b>BACKGROUND</b>To study the effect of human papillomavirus (HPV) 16 E6/E7 and TPA (12-O-tetradecanog-1-phorbol-13-acetate) on malignant transformation of human embryo oral tissue.</p><p><b>METHODS</b>Recombinant plasmid with HPV 16 E6/E7 was constructed and transfected into human embryo oral tissue. The oral tissue with HPV 16 E6/E7 gene or without the gene was inoculated into the hypophloeodal of right shoulder in scid mice, respectively. The study was conducted in four groups: the first group was the oral tissue transfected plasmid with HPV 16 E6/E7 plus TPA, which were inoculated into 8 scid mice; the second group was only oral tissue transfected with plasmid with HPV 16 E6/E7 into 6 scid mice; the third group was normal oral tissue plus TPA inoculated into 6 scid mice, and the final group was only normal oral tissue inoculated into 5 scid mice. Three days after inoculation, TPA was injected at the left shoulder of the mice once a week. Twelve weeks after inoculation, tumor was found in 7 scid mice from the first group. HPV 16 E6/E7 gene in tumor tissues was analyzed by PCR.</p><p><b>RESULTS</b>The rate of tumor formation was 7/8 in the first group; no tumor was found in the other groups. Pathological diagnosis of the tumor was fibrohistiocytoma. HPV 16 E6/E7 gene was detected by PCR in tumor tissues.</p><p><b>CONCLUSION</b>With the cooperating action of TPA, human oral tissue containing HPV 16 E6/E7 gene could cause malignant transformation in scid mice.</p>