Characteristics and prognosis of patients after resection of nonsmall cell lung carcinoma measuring 2 cm or less in greatest dimension

BACKGROUND: There remains ongoing controversy with regard to the optimal management strategy and the prognostic significance of small-sized nonsmall cell lung carcinoma. Therefore, in the current study, the authors analyzed the clinical characteristics of patients who underwent complete resection of these lung tumors, the follow-up data, and the significant prognostic factors. METHODS: Of 1726 consecutive patients surgically treated for proven primary lung carcinoma, 265 patients underwent complete removal of a nonsmall cell lung carcinoma in which the greatest dimension of the resected specimen was < or = 2 cm. RESULTS: The cancer-specific 5-year and 10-year survival rates were 86% and 83%, respectively. Univariate analyses revealed that advanced pathologic stage, a tumor size of 16-20 mm, lymphatic vessel invasion, vascular vessel invasion, a high serum level of carcinoembryonic antigen (CEA), and extended resection were significantly unfavorable prognostic factors. Among these factors, multivariate analyses demonstrated that pathologic stage (P < 0.0001), vascular vessel invasion (P = 0.0040), and CEA level (P = 0.0291) were significant, independent determinants of survival. None of the patients with pathologic Stage I disease, no vascular vessel invasion, and a low serum CEA level died of their disease after undergoing complete resection. CONCLUSIONS: The preoperative level of serum CEA and vascular vessel invasion by tumor cells were found to be independent prognostic factors that were as significant as the well established determinant of pathologic stage for patients with a nonsmall cell lung carcinoma measuring < or = 2 cm in greatest dimension. These data may contribute to the explanation of the lower-than-expected survival of patients after complete surgical resection of such a small-sized tumor.     

Conventional clinicopathologic prognostic factors in surgically resected nonsmall cell lung carcinoma. A comparison of prognostic factors for each pathologic TNM stage based on multivariate analyses

BACKGROUND: A number of prognostic factors have been reported for resected nonsmall cell lung carcinoma. None of them, however, has been reported to have greater prognostic impact than the pathologic TNM staging system. The authors evaluated 18 conventional clinicopathologic prognostic factors in each pathologic stage. METHODS: A retrospective study was conducted on surgically resected 836 lung carcinoma patients, and the following conventional prognostic factors were evaluated in multivariate analyses: age, gender, pack-year smoking, serum carcinoembryonic antigen and squamous cell carcinoma antigen levels, laterality of tumor, clinical N status, histologic type of tumor, greatest tumor dimension, grade of differentiation, pleural involvement, lymphatic invasion, vascular invasion, degree of fibrosing scarring, nuclear atypia, mitotic activity, and curativity of resection. RESULTS: The overall 5-year survival rate was 63.8%. In 430 cases of pathologic Stage I disease, multivariate analyses revealed 3 significant prognostic factors: clinical N status (P < 0.001), vascular invasion (P = 0.001), and curativity of resection (P < 0.001). In 406 cases of more advanced disease, i.e., pathologic Stage II, IIIA, IIIB, or IV, multivariate analyses revealed 4 factors as significant: histology (P = 0.001), pathologic N status (P < 0.001), tumor size (P < 0.001), and curativity of resection (P = 0.002). CONCLUSIONS: Conventional clinicopathologic prognostic factors had a different impact on prognosis in each pathologic TNM stage among patients who underwent surgical resection of nonsmall cell lung carcinoma. These factors should be analyzed separately in each pathologic TNM stage.     

Clinocopathologic significance of laminin-5 gamma2 chain expression in squamous cell carcinoma of the tongue: immunohistochemical analysis of 67 lesions.

BACKGROUND: The laminin-5 gamma2 chain plays an important role in cell migration during tumor invasion and tissue remodeling. METHODS: Laminin-5 gamma2 chain expression in squamous cell carcinomas of the tongue in 67 patients with Stage II, III, or IVA,B (excluding the cases with distant metastasis) was examined immunohistochemically to determine its associations with the clinicopathologic features of each tumor. The predominant staining patterns were categorized as follows: A, few or no tumor cells were positive; B, part of the tumor nest periphery was positive; C, the tumor nest periphery was circumferentially positive; or D, almost all the tumor cells were positive. RESULTS: Laminin-5 gamma2 chain expression was observed clearly in tumor cell cytoplasm. Of the 67 tumors examined, 6 (9%), 31 (46%), 19 (28%), and 11 (17%) showed staining patterns A, B, C, and D, respectively. With progression from staining pattern A to D, the number of immunopositive tumor cells increased significantly (P<0.0001), and the tumor histology showed significantly more infiltrative growth (P<0.0001) and poorer differentiation (P = 0.0021). Furthermore, both univariate (P = 0.0019) and multivariate (P = 0.0003; hazard ratio = 3.132) analysis of the patients' survival revealed that the prognosis became significantly poorer with progression from staining pattern A to D. CONCLUSIONS: Increased laminin-5 gamma2 chain immunoreactivity, which may reflect a high invasive potential of cancer cells, is a factor indicative of a poor prognosis for patients with squamous cell carcinoma of the tongue.     

Combined role of tumor angiogenesis, bcl-2, and p53 expression in the prognosis of patients with colorectal carcinoma.

BACKGROUND: The objective of this study was to evaluate intratumoral neoangiogenesis in Dukes Stage B and Stage C (AJCC/UICC Stage I and III) colorectal adenocarcinoma and its correlation with nuclear p53 oncoprotein accumulation and cytoplasmic bcl-2 expression as well as to assess the prognostic significance of these features in patient outcome. METHODS: Paraffin embedded specimens from 55 patients with Dukes Stage B (AJCC/UICC Stage I) and 51 patients with Dukes Stage C (AJCC/UICC Stage III) colorectal adenocarcinoma who were treated with surgery were assessed. Patients with lymph node involvement (Dukes Stage C [AJCC/UICC Stage III]) also were treated with postoperative pelvic radiotherapy and adjuvant chemotherapy with 5-fluorouracil and leucovorin with or without interferon-alpha. Immunohistochemistry was performed using the anti-CD31 monoclonal antibody (MoAb) for vessel staining, the DO7 MoAb for nuclear p53 expression, and the clone 124 for cytoplasmic/perinuclear bcl-2 expression. Patient follow-up ranged from 4-70 months (median, 28 months). RESULTS: High vascular grade (microvessel score [MS] >/= 40) was observed in 39 of 106 specimens (37%), a medium MS (16-39) was observed in 29 of 106 cases (27%), and a low MS (7-15) was observed in 38 of 106 cases (36%). Positive expression of the bcl-2 protein in > 10% of cells was observed in 33 of 106 cases (31%), whereas p53 nuclear oncoprotein accumulation in > 10% of cells occurred more frequently (44 of 106 cases [42%]). No correlation among p53 expression, bcl-2 expression, and vascular grade was observed. Stroma infiltration by CD31 positive lymphocytes was associated strongly with increased vessel density (P = 0.0001). In univariate analysis Dukes stage was the only significant prognostic parameter (P = 0.02), whereas p53 and vascular grade showed marginal prognostic significance (P = 0.07 and P = 0.09, respectively). In Dukes Stage C (AJCC/UICC Stage III) patients, high vascular grade was the only parameter that predicted a worse overall survival (P = 0.04). Double stratification showed that patients with high vascular grade and positive p53 expression had a poorer survival (P = 0.03). CONCLUSIONS: The results of the current study suggest that p53 mutations, loss of bcl-2 expression, and tumor angiogenesis are events linked to the processes of metastases and local invasion in patients with colorectal carcinoma. Increased vascularization appears to be the most important prognostic factor in patients with Dukes Stage C (AJCC/UICC Stage III) colorectal adenocarcinoma.     

Adenocarcinoma of the uterine cervix. Prognostic significance of pretreatment serum CA 125, squamous cell carcinoma antigen, and carcinoembryonic antigen levels in relation to clinical and histopathologic tumor characteristics

The prognostic value of the pretreatment serum CA 125, squamous cell carcinoma antigen (SCC), and carcinoembryonic antigen (CEA) levels in relation to tumor type, vascular invasion by tumor cells, and lymph node metastases was investigated in 77 patients with cervical adenocarcinoma. In Stage IB (International Federation of Gynecology and Obstetrics [FIGO]), the five-year actuarial survival of patients with pretreatment serum CA 125 levels greater than 16 U/ml was 52.4% versus 95.6% when normal serum CA 125 levels were determined (P less than 0.01). Pretreatment serum SCC or CEA levels had no substantial prognostic value. In Stage IB (FIGO), 42% of the patients with elevated serum CA 125 levels had lymph node metastases versus 4% when normal levels were found (P = 0.012). The presence of vascular invasion (P = 0.01) or lymph node metastases (P = 0.001) was associated with an increased risk for recurrent disease. Adenosquamous tumors showed a higher incidence of vascular invasion (P = 0.05) and a higher incidence of elevated serum CA 125 levels (P = 0.03). Particularly in Stage II, adenosquamous tumors were found to have a poorer prognosis than adenocarcinomas (P = 0.0566). We conclude that in cervical adenocarcinoma serum CA 125 is an important prognostic factor and an implicit indicator of tumor virulence.     

Expression of heparanase and its clinical significance in human non-small cell lung cancer

Objective： To explore the expression and significance of heparanase in non-small cell lung cancer （NSCLC） regarding prognosis and clinicopathological parameters. Methods： The expression of heparanase was assessed using immunohistochemistry staining and Western blot in 122 paraffin-embedded specimens and 38 freshly taken tissues. The relationship between heparanase expression and the clinicopathological factors was analyzed by Chi-square test, multivariate analysis and Kaplan-Meier method. Results： In the immunoreactive cells, staining was mainly located in cytoplasma and membrane. Human heparanase was highly expressed in lung cancer tissue （78.7%, 96/122） while negative in epithelia of normal lung tissues. The level of heparanase was remarkably higher in NSCLC than that in normal tissue （P=0.043）. Expression of heparanase significantly correlated with TNM stage （P=0.025）, lymphatic metastasis （P=0.002） and vascular invasion （P=0.0003）. The patients with positive heparanase expression had a significantly shorter survival than those with negative heparanase expression （P=0.0006）. In multivariate analysis, only p-TNM stage, lymphatic metastasis and vascular invasion could be considered as prognostic factors. Conclusion： Elevated level of heparanase in human non-small cell lung cancer tissues correlates with the TNM stage, invasion, metastasis and prognosis. However, heparanase expression is not an independent prognostic factor.     

Is vascular and lymphatic space invasion a main prognostic factor in uterine neoplasms with a sarcomatous component? A retrospective study of prognostic factors of 60 patients stratified by stages

: Sarcomatous neoplasms of the uterine corpus are still a challenge in terms of obtaining prognostic factors and the most optimum complementary treatment to surgery. The most important prognostic factor is stage; relapses usually appear during the first 2 years, and most patients die within the first 3 years. We have performed a multivariate study of prognostic factors, stratifying patients by stage, to determine their impact on overall survival, disease-free survival, local relapse-free survival, and distant metastasis-free survival. Special emphasis has been given to vascular and lymphatic space invasion (VLSI).

: Sixty patients diagnosed with uterine neoplasms with a main sarcomatous component were treated at Hospital Clínic i Universitari of Barcelona between January 1975 and June 1999. Pathologic type: 32 carcinosarcomas, 14 leiomyosarcomas, 9 adenosarcomas, and 5 endometrial stromal sarcomas. Treatment: 58/60 surgery, 35/60 postoperative radiotherapy, 2/60 exclusive chemotherapy, and 3/60 complementary chemotherapy. FIGO stages: 43 Stage I, 4 Stage II, 11 Stage III, and 2 Stage IV. Variables analyzed: age, stage, vascular and lymphatic space invasion, myometrial invasion, mitotic index, tumor size, unicentricity/multicentricity, necrosis, and radiotherapy. Statistics: the S and Cox proportional risk models. The partial effect of each risk factor was calculated by hazard ratio (HR) with a confidence interval of 95%.

: Early stages: Multivariate analysis showed that tumor size larger than 8 cm and VLSI had an impact on overall survival (HR = 4.01 and HR = 24.45, respectively). VLSI was present in 23% of the cases. Myometrial invasion greater than 50% had an impact on disease-free survival and local relapse-free survival (HR was 9.75 and 3.20, respectively). VLSI had an impact on distant metastasis-free survival (HR = 2.92). Advanced stages: VLSI was present in 89% of the cases. Only leiomyosarcoma type made the overall survival worse (HR = 10.54).

: Vascular and lymphatic space invasion was a relevant prognostic factor in our series, with an impact on overall survival and distant metastasis-free survival in early stages. In advanced stages, VLSI had no impact on survival, but was present in 89% of cases. Myometrial invasion >50% had an impact on local relapse. Advanced stages had a more aggressive behavior, and there was a higher incidence of poor prognostic factors in these stages. Nevertheless, prospective studies are still needed on prognostic factors and on the best treatment option.     

Overexpression of T-LAK cell-originated protein kinase predicts poor prognosis in patients with stage I lung adenocarcinoma

Tumor recurrence is the most common cause of disease failure after surgical resection in early-stage lung adenocarcinoma. Identification of clinically relevant prognostic markers could help to predict patients with high risk of disease recurrence. A meta-analysis of available lung adenocarcinoma microarray datasets revealed that T-LAK cell-originated protein kinase (TOPK), a serine/threonine protein kinase, is overexpressed in lung cancer. Using stable cell lines with overexpression or knockdown of TOPK, we have shown that TOPK can promote cell migration, invasion, and clonogenic activity in lung cancer cells, suggesting its crucial role in lung tumorigenesis. To evaluate the prognostic value of TOPK expression in resected stage I lung adenocarcinoma, a retrospective analysis of 203 patients diagnosed with pathological stage I lung adenocarcinoma was carried out to examine the expression of TOPK by immunohistochemistry (IHC). The prognostic significance of TOPK overexpression was examined. Overexpression of TOPK (IHC score >3) was detected in 67.0% of patients, and these patients were more frequently characterized with disease recurrence and angiolymphatic invasion. Using multivariate analysis, patient age (>65 years old; P = 0.002) and TOPK overexpression (IHC score >3; P < 0.001) significantly predicted a shortened overall survival. Moreover, TOPK overexpression (IHC score >3; P = 0.005) also significantly predicted a reduced time to recurrence in the patients. Our results indicate that overexpression of TOPK could predetermine the metastatic capability of tumors and could serve as a significant prognostic predictor of shortened overall survival and time to recurrence.     

Vascular Invasion as An Independent Prognostic Indicator in Radically Resected Non-small Cell Lung Cancer

Objective： A retrospective study was performed to analyze the impact of vascular invasion on prognosis in a series of radically resected non-small cell lung cancer （NSCLC） and the subgroup of T1-4 nodal negative NSCLC patients. Methods： A total of 259 NSCLC patients who had undergone radical resection were entered into this study. Detailed clinical data including five-year survival were obtained for all the patients. The tumors were reviewed for the presence or absence of vascular invasion. Fisher＇s exact tests were used to assess the relationship between vascular invasion and other clinicopathological variables. Survival time was defined as the interval from the date of operation to either death from lung cancer or the last follow-up. Univariate analysis of survival curve was performed by the Kaplan-Meier method using the Log rank test. Multivariate survival analysis was carried out by Cox regression. P〈0.05 was considered statistically significant. Results： In 259 patients, 33 cases were diagnosed as having vascular invasion. The overall 5-year survival was 37.5%. Patients with vascular invasion had a median survival of 20 months compared with 43 months for those without vascular invasion （P〈0.01）. Multivariate analysis indicated that vascular invasion was a significant independent prognostic predictor for shortened cancer-related survival in the patients. The relative risk for cancer-related survival was 2.2-fold greater in patients with vascular invasion （95% CI： 1.45-3.32）. Subgroup analysis revealed that patients with vascular invasion had a 5-year survival of 11.1% compared with 57.1% for those without vascular invasion in the resected lung cancer patients at T1-4N0M0 （P=0.002）. Conclusion： Vascular invasion can serve as an independent prognostic factor in radically resected NSCLC.     

Peritumoral lymphatic vessel density and vascular endothelial growth factor C expression in early-stage squamous cell carcinoma of the uterine cervix.

PURPOSE: Lymphatic invasion and nodal metastasis plays a major role in the spread of cervical cancer; however, little is known about the mechanisms whereby tumor cells enter the lymphatic system. EXPERIMENTAL DESIGN: We examined the intra- and peritumoral lymphatic vessel density (LVD) using D2-40 immunohistochemistry in 111 cervical squamous cell carcinomas and correlated them with vascular endothelial growth factor (VEGF)-C expression, clinicopathologic tumor features, and outcome. RESULTS: Compared with benign cervix, intratumoral and peritumoral LVD was significantly increased (P < 0.0001). Peritumoral LVD was significantly higher than intratumoral LVD (P = 0.009). High peritumoral, but not intratumoral, LVD showed significant correlation with high tumor stage, lymphatic invasion, and nodal metastasis. VEGF-C showed increased expression at the invasive edge compared with the center of tumors (P < 0.0001) and correlated with high peritumoral LVD, lymphatic invasion, and nodal metastasis. High peritumoral LVD and VEGF-C expression at the invasive edge of tumors were associated with poor overall and recurrence-free survival in univariate analysis. In multivariate analysis, peritumoral LVD was the only independent term predictive of overall survival. CONCLUSIONS: Our findings suggest a potential role for VEGF-C in tumor-induced lymphangiogenesis represented by high peritumoral LVD, which may be one of the mechanisms leading to lymphatic invasion and metastatic spread. High peritumoral LVD may be an independent prognostic factor in early-stage cervical cancer.     

Carbohydrate status detecting by PNA is changeable through cancer prognosis from primary to metastatic nodal site: A possible prognostic factor in patient with node-positive lung adenocarcinoma

Carbohydrates antigens in cancer cells are considered to be important molecules, which may play a critical role for metastasis. To elucidate the prognostic relevance of the expression of peanut agglutinin (PNA) binding carbohydrates in patients with lung adenocarcinoma, we investigated the PNA binding carbohydrates immunohistochemically in both of primary tumors and involving nodal lesions. A total of 62 patients with node-positive primary lung adenocarcinoma, who had undergone complete resection and regional nodes dissection were subjected to this study. There were no significant correlations between PNA staining rates and clinicopathological variables. The survival rate of patients who had positive PNA staining in both of primary tumor and nodal lesion was significantly higher than those of patients in the other groups. Furthermore, the loss of the staining rate of PNA was an independent prognostic factor beside the lymphatic vessel invasion using multivariate analysis. The expression of PNA binding carbohydrates in tumor tissue and nodal lesion would be a novel significant prognostic factor for patients with node-positive lung adenocarcinomas.     

Whole body FDG-PET for the evaluation and staging of small cell lung cancer: a preliminary study

PURPOSE: We conducted a randomized trial to investigate whether systematic nodal dissection (SND) is superior to mediastinal lymph nodal sampling (MLS) in surgical treatment of non-small cell lung cancer (NSCLC). METHODS: The patients resectable clinical Stage I-IIIA NSCLC were randomly assigned to lung resection combined with SND or lung resection combined with MLS. After postoperative pathological re-staging, eligible cases were followed up until 30 November 2000. The Kaplan-Meier method was used for survival analysis. COX proportional hazards model was used for prognostic analysis. RESULTS: Of the 532 patients who were enrolled in the study, 268 patients were assigned to lung resection combined with SND and 264 were assigned to lung resection combined with MLS. After surgical restaging only 471 cases were eligible for follow-up. The median survival was 59 months in the group given SND and 34 months in the group given MLS (P=0.0000 by the log rank test). There was significant difference in survival in Stage I (5-year survival 82.16 vs. 57.49%) and Stage IIIA (26.98 vs. 6.18%) by the log rank test and Breslow test. There was no significant yet marginal difference in survival by log rank test (10-year survival 32.04 vs. 26.92%, P=0.0523) but significant difference in survival by Breslow test (5-year survival 50.42 vs. 34.05%, P=0.0284) in Stage II. Types of mediastinal lymph node dissection, pTNM stage, tumor size and number of lymph node metastasis were four factors that influenced long-term survival rate by multivariate analysis. CONCLUSIONS: As compared with MLS, lobectomy (pneumonectomy) combined with SND can improve survival in resectable NSCLC.     

A multivariate analysis of blood vessel and lymph vessel invasion as predictors of ovarian and lymph node metastases in patients with cervical carcinoma

BACKGROUND: To the authors' knowledge there are few available data regarding the influence of lymphovascular space invasion, which has been examined separately as two components (lymphatic vessel invasion [LVI] and blood vessel invasion [BVI]), in the metastasis of cervical carcinoma. METHODS: LVI and BVI, which include capillary vessel invasion, were reviewed retrospectively based on the histopathologic slides of 239 women with cervical carcinoma who were treated with radical hysterectomy. The correlation between lymph node and/or ovarian metastases and LVI, BVI, and other histopathologic factors was investigated by multiple logistic regression analysis. The influence of LVI and BVI on survival was examined by Cox regression analysis. RESULTS: The rate of incidence of LVI was higher than that of BVI in all stages of cervical carcinoma (P < 0.0001 for International Federation of Gynecology and Obstetrics Stage IB and Stage II disease and P < 0.05 for Stage III disease). The incidence rate of BVI increased as LVI became more prominent and there was a significant correlation between the two findings (P < 0.0001). BVI was more frequent in adenocarcinoma/adenosquamous carcinoma than in squamous cell carcinoma (P < 0.05). LVI (P < 0.0001) and parametrial invasion (P < 0.0001) were significantly related to lymph node metastasis on multivariate analysis. Conversely, BVI (P < 0.05) and parametrial invasion (P < 0.0025), as well as adenocarcinoma or adenosquamous carcinoma (P < 0.0005), were significantly related to ovarian metastasis on multivariate analysis. With regard to the prognostic significance of these components, it was found that BVI (hazards ratio [HR] = 2.0), ovarian metastasis (HR = 6.5), and lymph node metastasis (HR = 5.5) were significantly related to a poor prognosis in women with cervical carcinoma. CONCLUSIONS: Ovarian metastasis may occur via hematogenous spread of cervical carcinoma. The results of the current study suggest that BVI, including capillary vessels, that is diagnosed separately from LVI using hematoxylin and eosin stained sections may be an important prognostic factor for patients with cervical carcinoma.     

Association between laminin-8 and glial tumor grade, recurrence, and patient survival

BACKGROUND: The authors previously sought to identify novel markers of glioma invasion and recurrence. Their research demonstrated that brain gliomas overexpressed a subset of vascular basement components, laminins, that contained the alpha4 chain. One of these laminins, laminin-8, was found to be present in highly invasive and malignant glioblastoma multiforme (GBM) (Grade 4 astrocytoma); its expression was associated with a decreased time to tumor recurrence, and it was found in vitro to promote invasion of GBM cell lines. METHODS: In the current study, the authors studied glial tumors of different grades in an attempt to correlate laminin-8 expression with tumor recurrence and patient survival. Immunohistochemistry and Western blot analysis were used to detect laminin isoforms of interest. RESULTS: Using immunohistochemistry and Western blot analysis, the authors confirmed high levels of laminin-8 expression in approximately 75% of the GBM cases examined and in their adjacent tissues, whereas astrocytomas of lower grades expressed for the most part a different isoform, laminin-9, which also was found in low amounts in normal brain tissue and benign meningiomas. Overexpression of laminin-8 in GBM was found to be associated with a statistically significant shorter time to tumor recurrence (P < 0.0002) and a decreased patient survival time (P < 0.015). CONCLUSIONS: The data suggest that laminin-8, which may facilitate tumor invasion, contributes to tumor regrowth after therapy. Laminin-8 may be used as a predictor of tumor recurrence and patient survival and as a potential molecular target for glioma therapy.     

Survival from synchronous bilateral breast cancer: the experience of surgeons participating in the breast audit of the Society of Breast Surgeons of Australia and New Zealand

Background: Previous studies generally indicate that synchronous bilateral breast cancers (SBBC) havean equivalent or moderately poorer survival compared with unilateral cases. The prognostic characteristics ofSBBC would be relevant when planning adjuvant therapies and follow-up medical surveillance. The frequency ofSBBC among early breast cancers in clinical settings in Australia and New Zealand was investigated, plus theirprognostic significance, using the Breast Cancer Audit Database of the Society of Breast Surgeons of Australiaand New Zealand, which covered an estimated 60% of early invasive lesions in those countries. Design: Rateratios (95% confidence limits) of SBBC were investigated among 35,370 female breast cancer cases by age ofwoman, histology type, grade, tumour diameter, nodal status, lymphatic/vascular invasion and oestrogen receptorstatus. Univariate and multivariable disease-specific survival analyses were undertaken. Results: 2.3% of caseswere found to be SBBC (i.e., diagnoses occurring within 3 months). The figure increased from 1.4% in womenless than 40 years to 4.1% in those aged 80 years or more. Disease-specific survivals did not vary by SBBC status(p=0.206). After adjusting for age, histology type, diameter, grade, nodal status, lymphatic/vascular invasion, andoestrogen receptor status, the relative risk of breast cancer death for SBBC was 1.17 (95% CL: 0.91, 1.51). Afteradjusting for favourable prognostic factors more common in SBBC cases (i.e., histology type, grade, lymphatic/vascular invasion, and oestrogen receptor status), the relative risk of breast cancer death for SBBC was 1.42(95% CL: 1.10, 1.82). After adjusting for unfavourable prognostic factors more common in SBBC cases (i.e.,older age and large tumour diameter), the relative risk of breast cancer death for SBBC was 0.98 (95% CL:0.76, 1.26). Conclusions: Results confirm previous findings of an equivalent or moderately poorer survival forSBBC but indicate that SBBC status is likely to be an important prognostic indicator for some cases.     

Modified scar grade: a prognostic indicator in small peripheral lung adenocarcinoma

BACKGROUND: Several studies have shown the prognostic value of desmoplasia for lung adenocarcinomas. The authors evaluated the density and extent of desmoplasia by modifying the scar grade, as well as the prognostic impact on patient survival. METHODS: Modified scar grade was defined as follows: Grade 1, no desmoplasia; Grade 2, sparse desmoplastic reaction; Grade 3, dense desmoplastic reaction with diameter of 10 mm or less; Grade 4, dense desmoplastic reaction with diameter exceeding 10 mm. In addition, the prognostic impact of conventional histologic factors and modified scar grade was analyzed in 239 cases of small peripheral lung adenocarcinoma (maximum dimension, 相似文献   

Laminin-332 promotes the invasion of oesophageal squamous cell carcinoma via PI3K activation

Laminin-332 is major component of epithelial basement membrane, and has an important role in cell migration and tumour invasion. Recently, the phosphatidylinositol 3-kinase (PI3K) activation induced by laminin-332 during carcinogenesis or tumour invasion has been highlighted in skin squamous cell carcinoma. The expression of laminin-332 in 126 resected oesophageal squamous cell carcinoma (ESCC) specimens was immunohistochemically examined to determine its associations with the clinicopathological characteristics, and the effect of laminin-332 on the invasiveness and the PI3K activation was assessed by in vitro experiments using ESCC cell lines (ESCCs). Sections with immunostaining signals in >30% cancer cells, which were observed in 55 of 126 cases, were judged to be positive for laminin-332. The positivity was significantly correlated with pTNM stage and poor prognosis. Inactivation of the PI3K pathway by laminin-332 blocking antibody suppressed the invasiveness of TE8 cell line, which secreted laminin-332 at high level and had high PI3K activity. The addition of the purified laminin-332 activated the PI3K pathway and increased the invasiveness of TE11 cell line, which secreted laminin-332 at lower level and had low PI3K activity. The deactivation of PI3K pathway using the PI3K inhibitor decreased the invasiveness of ESCCs and the secretion of laminin-332 in vitro. The expression of laminin-332 was one of the prognostic factors of ESCC. Laminin-332 could provide the autocrine positive-feedback loop through PI3K activation, contributing the invasive ability. Therefore, the inhibitor of PI3K pathway might be useful as the anticancer therapies for ESCC.     

肝素酶在人非小细胞肺癌组织中的表达研究

目的 探讨肝素酶(heparanase，Hpa)在人非小细胞肺癌组织中的表达及其与患者临床病理特征之间的关系，明确其对肺癌患者预后的意义。方法 采用免疫组织化学染色(S-P法)和Western blot检测122例人非小细胞肺癌石蜡包埋组织和38例新鲜肺癌组织及相应癌旁正常肺组织中肝素酶的表达情况，并用x^2检验、Cox比例风险模型和生存曲线等方法分析肝素酶在肺癌组织中的表达意义。结果 肝素酶主要表达在癌细胞膜和/或细胞浆中。免疫组织化学结果表明：在122例非小细胞肺癌组织中有96例(78．7%)呈肝素酶阳性表达，而癌旁正常支气管和肺泡上皮中无阳性表达。Westcrn blot结果亦证实肝素酶在肺癌叶的表达较癌旁正常肺组织明显增高(P=0．043)。x^2检验显示肝素酶表达与肺癌的临床分期(P=0．025)、淋巴结转移(P=0．002)和血管浸润(P=0．0003)有密切关系。生存曲线分析表明肝素酶阳性表达组患者的5年生存率明显低于阴性组(P=0．0006)。但多因素分析结果显示仅肺癌的分期、淋巴结转移和血管浸润可作为影响患者预后的风险因素。结论 肝素酶在人肺癌组织中的表达较正常肺组织明显上调，并与肺癌的临床分期、侵袭、转移和患者的预后相关，但不能作为患者预后评估的独立指标。     

Carbonic anhydrase IX expression is associated with tumor progression and a poor prognosis of lung adenocarcinoma

Carbonic anhydrase (CA) IX catalyzes the hydration of carbon dioxide into carbonic acid and participates in a variety of physiological and biological processes. The aim of this study was to evaluate the prognostic significance of CA IX expression in patients with lung adenocarcinoma. Standard immunohistochemical techniques were used to study CA IX expression in 134 patients who underwent curative resection for adenocarcinoma of the lung at our hospital between January 1995 and December 1996. We evaluated the correlations between CA IX expression levels on cancer cells and clinicopathological factors. CA IX expression was not observed in normal lung tissue or specimens from non-invasive adenocarcinomas. CA IX immunostaining was detected in 33 (24.6%) invasive adenocarcinoma cases. Poor differentiated histological phenotype (p=0.0015), pathological stage (p=0.0400), vascular invasion (p=0.0009) and lymphatic permeation (p=0.0050) were significantly related to CA IX expression. On univariate analysis, CA IX positive cases showed significantly shorter overall survival (p=0.0083) and disease-free survival (p=0.0122). In particular, the overall and disease-free survivals in stages I+II were significantly shorter in the CA IX positive than in the CA IX negative cases (p=0.0269 and 0.0011, respectively). Our results suggest that CA IX expression is strongly associated with tumor progression and indicates a poor prognosis for patients with stages I+II lung adenocarcinoma.