Comparison of Epidermal Growth Factor Receptor Gene Mutations Identified Using Pleural Effusion and Primary Tumor Tissue Samples in Non-Small Cell Lung Cancer.

BACKGROUND: Although the use of pleural effusion samples for epidermal growth factor receptor (EGFR) testing in lung cancer is increasing, the accuracy rate and effectiveness of identifying EGFR mutations using these samples, rather than primary tumor tissue samples, is not established. MATERIALS AND METHODS: One hundred ninety-two advanced, non-small cell lung cancer patients were enrolled into this study. All patients had primary tumor tissue and corresponding pleural effusion samples, and we employed the Amplification Refractory Mutation System to detect EGFR gene mutations in these samples. RESULT: The number of EGFR mutations detected in primary tumor tissue and pleural effusion samples was 119 (61.98%) and 113 (58.85%), respectively. The EGFR-mutation rate was significantly higher in female than in male patients, and in adenocarcinoma than in nonadenocarcinoma patients (P=0.000). Single mutations in exons 19 and 21 were the predominant observed mutation type, and the overall concordance rate of EGFR-mutation status between the 192 matched pleural effusion and primary tumor tissue samples was 86.98%. CONCLUSIONS: We observed a high concordance rate between EGFR mutations identified using primary tumor tissue and corresponding pleural effusion samples by Amplification Refractory Mutation System. Thus, it is likely that pleural effusion sampling from advanced non-small cell lung cancer patients, especially those with adenocarcinoma, may be effective in EGFR-mutation screening.

The Expression Pattern of p120-Catenin is Associated With Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer.

BACKGROUND: Previous research connects p120-catenin (p120ctn) with epidermal growth factor receptor (EGFR) signaling pathways, which presents a potential role for p120ctn in EGFR tyrosine kinase inhibitor (EGFR-TKIs) resistance. However, a direct correlation between the expression pattern of p120ctn in solid tumors and the therapeutic effect of EGFR-TKIs has not yet been demonstrated. METHODS AND RESULTS: In this study, the expression pattern of p120ctn was examined in patients with the EGFR gene mutation in lung adenocarcinoma, and p120ctn was found to have different patterns of expression even in the same mutation type. The therapeutic effect of EGFR-TKIs was investigated in these patients, and patients with an abnormal expression of p120ctn were found to be more likely to have drug resistance. A gefitinib-resistant lung cancer cell line was established and alterations in the p120ctn expression pattern were also observed in vitro. CONCLUSIONS: Therefore, this study demonstrates that the expression pattern of p120ctn is associated with acquired resistance to EGFR-TKIs in lung cancer, providing information toward addressing the problem of drug resistance in patients with non-small cell lung cancer.

Synchronous of gastric adenocarcinoma and schwannoma: report of a case and review of literatures.

We presented a case of 80-year-old male with long term stomachache, marasmus and anaemia. Endoscopic evaluation suggested the malignant ulcerative tumor on the Gastric antrum, and biopsy confirmed the diagnosis of gastric adenocarcinoma. Surprisingly, in resected specimen the pathologist found a nodule just below the ulcer with clear boundary and gray-yellow section. Histologically, the whole lesion was composed with adenocarcinoma area and spindle tumor cells area. In the spindle tumor cells area, the cells with round or oval nuclei, eosinophilic cytoplasm, and these cells showed bundle or fence-like arrangement. Immunohistochemistry study presented positive expression of vimentin, S-100 and GFAP, negative expression of SMA, desmin, CD34, CD117 and Dog-1, which suggested the diagnosis of co-occurrence of gastric adenocarcinoma and schwannoma. To our knowledge, it is an extremely rare case that only two cases have been reported.

Mesothelioma of the tunica vaginalis testis with prominent adenomatoid features: a case report.

Malignant mesotheliomas of the testis arise from the tunica vaginalis, formed from the evagination of the abdominal peritoneum into the scrotum. It is an extremely rare tumor representing 0.3% to 5% of all malignant mesotheliomas. We presented an interesting case of 68-year-old male with swelling and slightly painful in the right scrotum. Histologically, the lesion were composed of small tubular, microcystic, gland lined by flattened epithelioid cells and vague signet ring cells set in a myxofibrous stroma, which is resemblance to adenomatoid tumor. But the tumor cells showed significant atypical cytologic morphology and invaded into spermatic cord tissue, which indicated the diagnosis of malignant tumor. Immunohistochemistry study showed positive expression of CK, CK5/6, CK7, Calretinin, D2-40 and Vimentin which indicated the diagnosis of malignant mesothelioma. This case of mesothelioma should be classified as epithelial in type. To our knowledge, the mesothelioma of the tunica vaginalis testis with adenomatoid tumor-like microscopic features is very rare.

Malignant solitary fibrous tumor of breast: a rare case report.

Solitary fibrous tumor (SFT) is rare mesenchymal neoplasm that has been originally and most often documented in the pleura. Recently, the ubiquitous nature of the SFT has been recognized with reports of involvement of numerous sites all over the body such as: upper respiratory tract, somatic tissue, mediastinum, head, and neck. Less than 10 cases SFT of breast have been reported. Herein, we presented a 52-year-old Asian female with SFT of breast, this tumor showed predominant malignant features. To our knowledge, SFT of breast with such malignant evidence is extremely rare.

Expression of a phosphorylated form of ATF4 in lung and non-small cell lung cancer tissues.

ATF4 is a member of the cAMP-responsive element-binding protein family of basic zipper-containing proteins, a family of transcription factors phosphorylated at serines residues by protein kinase A. The family has been proved to be able to stimulate the transcription of the genes containing CRE elements. Elevated ATF4 expression was detected in some tumors including breast carcinoma compared to their corresponding nontumor tissues. p-ATF4 (ser 245), a phosphorylated form of ATF4 protein at serine 245 site, was believed to be an active type of this protein. However, its expression and clinical significance in malignant tumors including non-small cell lung cancer were not reported up to date. In the current study, we investigate the expression of p-ATF4 (ser 245) in non-small cell lung cancer using tissue microarray and immunohistochemistry. p-ATF4 (ser 245) immunostaining was detected in nucleus and cytoplasm in cancer cells and normal lung epithelial cells. Compared to bronchial epithelium and submucosal glands (total positive rate, 14.6% (12/82)), there was increased expression of p-ATF4 (ser 245) in non-small cell lung cancer cells (total positive rate, 42.7% (35/82)) (p < 0.05). In addition, increased expression of p-ATF4 (ser 245) was associated with lymph node metastasis and advanced TNM stages (III and IV) in non-small cell lung cancer (p < 0.05). Immunofluorescent staining confirmed nuclear and cytoplasmic expression of p-ATF4 (ser 245) in lung and cancer tissues, and also in non-small cell lung cancer cell lines including NCI-H157 and LTE cells. These results indicate that increased expression of p-ATF4 (ser 245) may contribute to cancer development of non-small cell lung cancer and may be a potential cancer marker.

Mediastinal epithelioid hemangioendothelioma with abundant spindle cells and osteoclast-like giant cells mimicking malignant fibrous histiocytoma.

Epithelioid hemangioendothelioma is a relatively uncommon lesion usually presenting in soft tissues. The occurrence in the mediastinum is exceptional rare. Histologically, this tumor is characterized by epithelioid cells with intracytoplasmic vacuoles in a hyalinized or mucinous stroma. Occasionally, spindle cells or osteoclast-like giant cells can be observed. Herein, we present a case of epithelioid hemangioendothelioma in a 38 year-old Chinese male. The tumor was predominantly composed of abundant spindle cells with marked atypia and scattered osteoclast-like giant cells reminiscent of malignant fibrous histiocytoma. The unusual histological appearance can pose a great diagnostic challenge. It may be easily misdiagnosed, especially if the specimen is limited or from fine-needle aspiration.

A case of adenocarcinoma of the rete testis accompanied by focal adenomatous hyperplasia.

Adenocarcinoma of the rete testis is very rare. There is still little knowledge about its etiology and pathogenesis. Herein, we present a case of rete testis adenocarcinoma in a 36-year-old Chinese male. The tumor was predominantly composed of irregular small tubules and papillary structures with cuboidal or polygonal cells. In peripheral area of the tumor, the remaining normal rete testis and adenomatous hyperplasia of the rete testis could also be seen, indicating the possible relationship between adenomatous hyperplasia and adenocarcinoma. In addition, the patient underwent a left hydrocelectomy because of the existence of hydrocele 3 years ago. But, it is unclear whether hydrocele and hydrocelectomy is its cause or just the early clinical presentation of the adenocarcinoma.

Endobronchial endometriosis presenting as central-type lung cancer: a case report.

A 45-year-old female patient was referred to our hospital for complaining of dyspnea and coughing in the past four months. The computed tomography scanning demonstrated a central lesion in the upper lobe of the left lung close to the hilar, and the subsequent bronchoscopy revealed a polypoid lesion of the distal of the left main bronchus. This patient was diagnosed clinically as "possibly central-type lung cancer". However, the pathologic result of the surgically excised polypoid lesion was endobronchial endometriosis. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1077439085928525.

Overexpression of NEDD9 is associated with altered expression of E-Cadherin, ß-Catenin and N-Cadherin and predictive of poor prognosis in non-small cell lung cancer.

Neural precursor cell expressed, developmentally down-regulated 9 (NEDD9) is overexpressed in multiple tumor types, where it is thought to regulate tumor cell metastasis and act as a trigger of the epithelial-mesenchymal transition (EMT). Loss of E-cadherin/ß-catenin and upregulation of N-cadherin are hallmarks of the EMT. The expression and correlation of NEDD9 with E-cadherin, ß-catenin and N-cadherin in lung cancer are poorly characterized. We examined NEDD9, E-cadherin, ß-catenin and N-cadherin protein expression in 105 cases of non-small cell lung carcinoma (NSCLC), including 43 cases of squamous cell carcinoma and 62 cases of lung adenocarcinoma, and the corresponding normal lung tissues using immunohistochemistry. NEDD9 was overexpressed in 56.2 % (59/105) of the NSCLC samples compared to normal lung tissue. Overexpression of NEDD9 correlated with abnormal expression of E-cadherin, ß-catenin and N-cadherin (P < 0.001, P = 0.008 and P = 0.027, respectively). Additionally, overexpression of NEDD9 correlated positively with lymph node metastasis in NSCLC (Chi-square test; P = 0.015). The mean overall survival of NSCLC patients overexpressing NEDD9 (39.10 ± 6.49 months) was markedly shorter than patients with normal NEDD9 expression (56.67 ± 7.44 months; Log-Rank, P = 0.001). Moreover, for patients with adenocarcinoma or squarmous cell carcinoma, the survival is also dramatically poorer upon overexpression of NEDD9. In multivariate analysis, overexpression of NEDD9 (P = 0.013) and TNM stage (P = 0.001) were significant independent prognostic factors for overall survival in NSCLC. In conclusion, overexpression of NEDD9 correlates with altered expression of EMT markers, increased lymph node metastasis and poorer survival in lung cancer.

Pulmonary sclerosing hemangioma presenting with dense spindle stroma cells: a potential diagnostic pitfall.

Pulmonary sclerosing hemangioma (PSH) is an uncommon pulmonary tumor. Histologically, PSH typically consists of two types of cells, surface cuboidal cells and polygonal cells, four architectural patterns including papillary, sclerotic, solid, and hemorrhagic. Herein, we present a case of PSH in a 59-year-old Chinese female. The tumor was predominantly composed of solid area presenting with diffuse spindle cells rather than polygonal cells. Focally, classical papillary and sclerotic area could be seen. Immunohistochemical staining showed that the spindle cells were positive for TTF-1, EMA, Actin(SM) and Vimentin, and negative for cytokeratin, cytokeratin7, cytokeratin5/6, surfactant apoprotein A, surfactant apoprotein B, CD34, CD99, S-100, HMB45, Desmin, Synaptophysin, CD56, ALK and Calretinin. The immunophenotype of the dense spindle cells in this case was similar to that of the polygonal cells, and thus the spindle cells may be the variants of polygonal cells. Based on morphologic features and the immunohistochemical profile, the tumor was diagnosed as a PSH. The significance of spindle cells change is unclear for us. To our knowledge, this is the first reported case of PSH showing dense spindle cells in solid area. This case represents a potential diagnostic pitfall, as it may be misdiagnosed as a mesenchymal tumor such as inflammatory myofibroblastic tumor, synovial sarcoma, solitary fibrous tumor, leiomyoma, or even mesothelioma, especially if the specimen is limited or from fine- needle aspiration. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1235401622806126.

Expression of p130cas, E-cadherin and ß-catenin and their correlation with clinicopathological parameters in non-small cell lung cancer: p130cas over-expression predicts poor prognosis.

p130cas (p130 Crk-associated substrate) is a scaffolding protein and plays an important role in regulating focal adhesion and driving cell migration. Also, the destruction of E-cadherin/ß-catenin adhesive complex is one of the changes that characterizes the invasive phenotype of tumors. The aim of this study is to evaluate the role of p130cas, E-cadherin, and ß-catenin expression in patients with non-small cell lung cancer (NSCLC). We examined the expression of p130cas, E-cadherin, and ß-catenin in 105 lung cancer tissues and paired adjacent normal lung tissues using immunohistochemistry. The overexpression of p130cas was observed in 61.9% (65/105) of lung cancer samples. The overexpression of p130cas was correlated with abnormal expression of E-cadherin and ß-catenin (P=0.002 and P=0.006, respectively). Chi-square test showed that the overexpression of p130cas correlated positively with lymph node metastasis and high TNM stage. The Log-Rank test revealed that the mean survival time of patients with p130cas overexpression (36.31 ± 5.66 months) was markedly shorter than those with p130cas normal expression (60.57 ± 6.95 months). Multivariable analysis indicated p130cas overexpression (P<0.001) as an independent significant prognostic factor for NSCLC patients' survival. These results indicate that p130cas may impact a variety of clinicopathological features of NSCLC and may y influence the prognosis of lung cancer patients.

Expression and significance of stem cell markers in pulmonary sclerosing haemangioma.

AIMS: The two major types of cells of pulmonary sclerosing haemangioma (PSH) with the same origin show significant differences in morphological phenotype. Whether these differences are caused by their different differentiation status is still uncertain. The aim of this study was to analyse their differentiation status by detecting the expression of several stem cell markers in PSH. METHODS AND RESULTS: The expression of stem cell markers was examined by using streptavidin peroxidase (SP) immunohistochemisty in 45 PSH specimens. Also, the two types of cells were, respectively, captured by laser capture microdissection (LCM) from 28 PSH specimens, and total RNA was then extracted followed by reverse transcription-polymerase chain reaction (RT-PCR). The results demonstrated that the expression rates of ABCG2, Notch1 and Notch3 in polygonal cells were significantly higher than those in cuboidal cells (P < 0.05), and the expression levels of ABCG2, Notch3 and Jagged1 in polygonal cells were clearly higher than those in cuboidal cells (P < 0.05). CONCLUSION: The data obtained provided evidence that the two types of cells in PSH may be different in differentiation status. The differentiation difference between the two types of cells might lead to variation in their morphological phenotype.

In pulmonary sclerosing hemangioma expression of ß-catenin, Axin, and C-myc differs between the two cell types.

Previous studies have shown that pulmonary sclerosing hemangioma is a tumor derived from primitive respiratory epithelium, but its character and the differentiation status of the two cell types (polygonal and cuboidal) composing the lesion are still controversial. We hypothesize that the polygonal cells are immature compared with cuboidal cells and have higher proliferative activity. To further study this question, we examined the expression of ß-catenin, Axin, and C-myc by immunostaining in 45 primary sclerosing hemangioma (PSH) specimens. The two cell types were captured by laser capture microdissection from 28 PSH specimens, and total RNA was extracted. Messenger RNA (mRNA) expression of Axin and C-myc was examined by reverse transcription polymerase chain reaction (RT-PCR). By immunostaining, ß-catenin was predominantly strongly expressed on the cell membrane of cuboidal cells, while in polygonal cells, ß-catenin was predominantly expressed in the cytoplasm and significantly decreased on cell membranes. Axin was expressed in cuboidal cells in 93 % of our 45 cases, but only expressed in 18 % of these in polygonal cells. C-myc expression in polygonal cells was significantly stronger than in cuboidal cells (P < 0.05). RT-PCR showed that the expression level of Axin mRNA in cuboidal cells was significantly higher than in polygonal cells (P < 0.05), and expression level of C-myc mRNA in polygonal cells was significantly higher than in cuboidal cells (P < 0.05).The two PHS cell types have distinct expression of ß-catenin, Axin, and C-myc, suggesting that their differentiation status may be different. The higher expression of C-myc in polygonal cells suggests that these cells might have higher proliferative activity.

Elevated p-CREB-2 (ser 245) expression is potentially associated with carcinogenesis and development of breast carcinoma.

CREB-2, also known as ATF-4, belongs to the CREB proteins, a family of transcription factors phosphorylated at serine residues by protein kinase A (PKA). This family is known to stimulate the transcription of genes containing CRE elements. Recently, some studies have demonstrated elevated CREB-2 expression in certain tumor types, including breast carcinoma, compared to their corresponding non-tumor tissues. However, the expression and clinical significance in malignant tumors, including breast carcinoma, of p-CREB-2 (ser 245), a phosphorylated form of the CREB-2 protein at serine 245 site, which is believed to be an active type of this protein, have not been clearly documented. In the present study, we investigated the expression of p-CREB-2 (ser 245) in a group of tumor and non-tumor breast tissues, including normal breast epithelia, hyperplasia, dysplasia, carcinoma in situ and infiltrating carcinoma of the breast using tissue microarray and immunohistochemistry (IHC). p-CREB-2 (ser 245) immunostaining was detected in the nucleus and cytoplasm of these tissues. Compared to normal breast epithelia and breast hyperplasia (total positive rate 13.3%), there was increased expression of p-CREB-2 (ser 245) in dysplasia, carcinoma in situ (total positive rate 35.7%) and infiltrating carcinoma of the breast (total positive rate 60.0%) (p<0.05). The highest expression of p-CREB-2 (ser 245) was found in infiltrating breast carcinoma (total positive rate 60%) compared to normal breast epithelia and all types of non-infiltrating lesions (total positive rate 27.6%) (p<0.05). In addition, increased expression of p-CREB-2 (ser 245) was found to be associated with lymph node metastasis in infiltrating breast carcinoma (p<0.05). Immunofluorescent staining confirmed stronger staining of p-CREB-2 (ser 245) in breast cancer MCF 7 and MDA-MB-231 cells compared with normal breast epithelial MCF 10A cells. Western blotting revealed elevated expression levels of p-CREB-2 (ser 245) in 17 cases of breast carcinoma compared with corresponding normal breast tissues (p<0.05). These results indicate that elevated expression of p-CREB-2 (ser 245) may potentially contribute to carcinogenesis and cancer development of breast carcinoma.

Increased N-myc downstream-regulated gene 1 expression is associated with breast atypia-to-carcinoma progression.

N-myc downstream-regulated gene-1 (NDRG1) has been identified as a protein involved in the differentiation of epithelial cells. As a newly metastasis suppressor gene, whether it contributes to carcinogenesis of breast cancer is still unknown. This study aimed to clarify the possible role of NDRG1 for breast cancer carcinogenesis, and further to investigate its clinicopathological significance in invasive breast cancer. We examined the expression of NDRG1 in normal epithelium of breast (n = 35), usual ductal hyperplasia (n = 22), atypical ductal hyperplasia (n = 33), atypical lobular hyperplasia (n = 8), ductal carcinoma in situ (n = 16), lobular carcinoma in situ (n = 6), invasive ductal carcinoma (n = 50), and invasive lobular carcinoma (n = 45) by immunohistochemistry and analyzed the correlation between NDRG expression and clinicopathological features of invasive breast cancer. Western blot analysis was carried out to investigate the expression of NDRG1 in 20 invasive ductal breast cancer and the paired non-tumor portion of the same case. NDRG1 expression in invasive breast cancer (70/95, 73.7%) was higher than that in noninvasive breast lesions (29/85, 34.1%; p < 0.05) which was higher than that in normal breast epithelium (5/35, 14.3%; p < 0.05). Statistical analysis revealed a significant correlation between NDRG1 expression with tumor stage in invasive breast cancer, and its expression in invasive ductal carcinoma is significantly higher than invasive lobular carcinoma (p < 0.05). It was not associated with age, menopausal status, tumor size, and lymph node metastasis. NDRG1 protein levels were significantly higher in invasive ductal breast cancer compared to the paired non-tumor portion of the same case by Western blot analysis (p < 0.05). Increased NDRG-1 expression is associated with breast atypia-to-carcinoma progression. NDRG1 expression might participate in the carcinogenesis and progression of invasive breast cancer. These findings provide further evidence that NDRG1 may serve as an important biomarker for invasive breast cancer.

MTA1 expression correlates significantly with cigarette smoke in non-small cell lung cancer.

Metastasis tumor antigen 1 (MTA1), a novel candidate metastasis-associated gene, is known to increase the migration and invasion of various tumor cells in vitro. Expression of MTA1 has been shown to be closely correlated with aggressiveness in a variety of human cancers including non-small cell lung cancer (NSCLC). Cigarette smoke is the most established risk for lung carcinogenesis; however, its effects on the progression of NSCLC are still unclear. In this study, we investigated MTA1 expression and analyzed its association with cigarette smoke in NSCLC by immunohistochemistry. To gain a deeper insight into the molecular mechanism underlying the relation between MTA1 and cigarette smoke, we treated the NSCLC cell lines with cigarette smoke extract (CSE). MTA1 mRNA levels and proteins were detected in NSCLC cell lines via reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analysis. Matrigel invasion assay was performed to evaluate cell invasive ability with the treatment of CSE. Immunohistochemical analysis showed MTA1 expression in NSCLC (61/96, 63.5%) was higher than that in adjacent normal lung tissues (15/96, 15.6%; p < 0.05). Moreover, it was significantly associated with smoking history (p < 0.05). The results of RT-PCR and western blotting showed the upregulation of MTA1 after the treatment of CSE in NSCLC cell lines. Matrigel invasion assays showed that MTA1 upregulation and cell invasion was accompanied with the treatment of CSE in the NSCLC cell lines. MTA1 expression correlated with cigarette smoke in NSCLC and suggested that it may play an important role in the smoked-related progress of NSCLC.

Overexpression of Frat1 correlates with malignant phenotype and advanced stage in human non-small cell lung cancer.

Frat1 has been reported to be overexpressed in several human malignant tumors, including esophageal squamous, cervical, breast, and ovarian carcinoma, but the role of Frat1 in lung cancer is unknown. Our purpose is to investigate the expression of Frat1 and its correlation with clinicopathologic features and prognosis in lung cancer patients. Immunohistochemistry was performed on 137 cases of non-small cell lung cancer (NSCLC), including 78 cases with clinical follow-up, and Western blot and reverse transcription-polymerase chain reaction (RT-PCR) assays were performed to detect the protein and mRNA expression levels in 30 NSCLC and autologous matched normal tissues. In addition, lung cancer cell line A549 was transfected with Frat1-siRNA plasmids and Matrigel invasive assay was carried out to study the function of Frat1 in cancer cell invasiveness. The results showed that Frat1 was expressed in 85 (62.04%) cases of NSCLC by immunohistochemistry, while all 30 specimens of normal lung tissues were negative. Western blot and RT-PCR results for Frat1 mRNA were in agreement with immunohistochemical findings. Of interest, the expression of Frat1 was strongly correlated with tumor differentiation, TNM stage, and lymph node metastasis (P < 0.05). The Kaplan-Meier survival analysis demonstrated that the cases with Frat1 expression had significantly shorter survival than those without Frat1 (P < 0.001). In addition, down-regulation of Frat1 expression reduced the invasive ability in the A549 cell line, further supporting the idea that Frat1 may play a crucial role in carcinogenesis, tumor invasiveness and dissemination in human lung cancer.

A multiple marker analysis of apoptosis-associated protein expression in non-small cell lung cancer in a Chinese population.

A failure to undergo apoptosis is widely thought to be an important event in cancer formation and progression. Although there have been many studies in vitro that provide evidence for this suggestion, the roles of apoptosis-associated proteins in cancer tissues in vivo are not as yet fully understood. Moreover, multiple marker analyses of apoptosis-associated protein expression in non-small cell lung cancer (NSCLC) tissues are scarce. In the present study, we investigate the expression of a group of apoptosis-associated proteins including bcl-2, caspase-3, fas, fas ligand (fasL) and survivin, and its clinical significance in NSCLC tissues using immunohistochemistry (IHC). Bcl-2 staining in cancer tissue cells was found in cytoplasm and the positive rate was 38.2% (29/76). Caspase-3 staining was mainly seen in cytoplasm of cancer tissue cells (53.9% [41/76]) with a few cases of nuclear staining (6.6% [5/76]). Fas staining was seen in cytomembrane (15.8% [12/76]) and cytoplasm (42.1% [32/76]) of cancer tissue cells. Likewise, fasL also showed staining in cytoplasm (55.3% [42/76]) and cytomembrane (44.7% [34/76]) of cancer tissue cells. Survivin staining was seen in cytoplasm but not nuclear of cancer tissue cells and the positive rate was 48.7% (37/76). Higher cytoplasm expression of bcl-2 was associated with large tumor size (≥ 3 cm) in NSCLC (p < 0.05). Decreased cytoplasm expression of fas was associated with poor grade in NSCLC (p < 0.05). A negative correlation was found between bcl-2 and cytoplasm caspase-3 expression in NSCLC (p < 0.001). No separate expression of the apoptosis-associated proteins in NSCLC was linked to overall survival of patients (p > 0.05). Multiple marker analyses revealed caspase-3+/cytomembrane fasL- to be linked to better survival of patients with NSCLC (p < 0.05). These results indicate that apoptosis- -associated proteins may impact a variety of clinicopathological features of NSCLC and may co-operatively influence the prognosis of patients with this malignant tumor.

p53 nuclear accumulation and ERalpha expression in ductal hyperplasia of breast in a cohort of 215 Chinese women.

INTRODUCTION: Women with ductal hyperplasia including usual ductal hyperplasia (UDH) and atypical ductal hyperplasia (ADH) have an increased risk of developing invasive ductal carcinoma (IDC) of breast. The importance of several molecular markers in breast cancer has been of considerable interest during recent years such as p53 and estrogen receptor alpha (ERalpha). However, p53 nuclear accumulation and ERalpha expression have not been assessed in ductal hyperplasia co-existing with ductal carcinoma in situ (DCIS) or IDC versus pure ductal hyperplasia without DCIS or IDC. MATERIALS AND METHODS: We investigated p53 nuclear accumulation and ERalpha expression in breast ductal hyperplasia in a cohort of 215 Chinese women by immunohistochemistry (IHC), which included 129 cases of pure ductal hyperplasia, 86 cases of ductal hyperplasia co-existing with DCIS (41 cases) or IDC (45 cases). RESULTS: Nuclear p53 accumulation was identified in 22.8% of ADH (31/136), 41.5% of DCIS (17/41) and 42.2% of IDC (19/45), and no case of UDH (0/79). No difference in nuclear p53 accumulation was observed between pure ADH and ADH co-existing with DCIS (ADH/DCIS) or IDC (ADH/IDC) (P>0.05). The positive rate of ERalpha expression was lower in ADH (118/136, 86.8%) than that in UDH (79/79, 100%) (P<0.001), but higher than that in DCIS (28/41, 68.3%) or IDC (26/45, 57.8%) respectively (P<0.001). The frequency of ERalpha expression was lower in ADH/DCIS (23/29, 79.31%) and ADH/IDC (23/30, 76.67%) than that in pure ADH (72/77, 93.51%) respectively (P<0.05). There was a negative weak correlation between p53 nuclear accumulation and ERalpha expression as for ADH (coefficient correlation -0.51; P<0.001). CONCLUSIONS: Different pathological types of ductal hyperplasia of breast are accompanied by diversity in patterns of nuclear p53 accumulation and ERalpha expression. At least some pure ADH is molecularly distinct from ADH/CIS or ADH/IDC which indicated the two types of ADH are molecularly distinct entities although they have the same morphological appearance.