Prognostic factors in invasive bladder carcinoma in a prospective trial of preoperative adjuvant chemotherapy and radiotherapy

Clinical and pathologic factors were analyzed in 40 patients with localized muscle-invasive bladder carcinoma treated in a prospective bladder-preserving program consisting of transurethral tumor resection, neoadjuvant chemotherapy (methotrexate, cisplatin, and vinblastine [MCV]), and 4,000 cGy radiotherapy with concurrent cisplatin. Patients with biopsy-proven complete response after chemotherapy and 4,000 cGy radiation received full-dose radiotherapy (6,480 cGy) with cisplatin. Cystectomy was recommended to patients with residual disease. Distant metastasis rate was associated with tumor stage and size: 0% in T2 patients, 39% in T3-4 patients (P = .035), 6% for tumors less than 5 cm, and 59% for tumors greater than or equal to 5 cm (P = .002). Risk of bladder tumor recurrence was higher in patients with tumor-associated carcinoma in situ (CIS; 40%) than those without CIS (6%; P = .075). Papillary tumors and solid tumors both had similar treatment outcomes. By multivariate analysis, tumor stage T2 (P = .04) and absence of CIS (P = .03) were significant predictors of complete response; CIS was predictive of local bladder recurrence (P = .07); and tumor size (P = .03), response after chemoradiotherapy (P = .02), and vascular invasion (P = .08) were associated with distant metastasis. Six of eight local bladder tumor recurrences were superficial tumors. The low actuarial distant metastasis rate of T2 patients (0% at 3 years), the 3-year actuarial overall survival rates for T2 (89%) and T3-4 (50%) patients, and the similar treatment outcomes for papillary versus solid tumors are encouraging when compared with published historical controls. These results provide preliminary evidence (median follow-up, 30 months) that the current chemoradiotherapy regimen may have beneficial effects in the treatment of muscle-invasive bladder carcinoma. The true efficacy of neoadjuvant chemotherapy remains to be proven by ongoing randomized trials.     

The relationship between the systemic inflammatory response, tumour proliferative activity, T-lymphocytic infiltration and COX-2 expression and survival in patients with transitional cell carcinoma of the urinary bladder

The relationship between the systemic inflammatory response, tumour proliferative activity, T-lymphocytic infiltration, and COX-2 expression and survival was examined in patients with transitional cell carcinoma of the urinary bladder (n=103). Sixty-one patients had superficial disease and 42 patients had invasive disease. Cancer-specific survival was shorter in those patients with invasive compared with superficial bladder cancer (P<0.001). On univariate analysis, stratified by stage, increased Ki-67 labelling index (P<0.05), increased COX-2 expression (P<0.05), C-reactive protein (P<0.05) and adjuvant therapy (P<0.01) were associated with poorer cancer-specific survival. On multivariate analysis of these significant factors, stratified by stage, only C-reactive protein (HR 2.89, 95% CI 1.42-5.91, P=0.004) and adjuvant therapy (HR 0.29, 95% CI 0.14-0.62, P=0.001) were independently associated with poorer cancer-specific survival. These results would suggest that tumour-based factors such as grade, COX-2 expression or T-lymphocytic infiltration are subordinate to systemic factors such as C-reactive protein in determining survival in patients with transitional cell carcinoma of the urinary bladder.     

Adjuvant intravesicular pharmacotherapy for superficial bladder cancer.

In 1990, bladder cancer, excluding carcinoma in situ, was estimated to contribute 49,000 cases of cancer. In men 75 years old or older, it became the fifth leading cause of cancer deaths. Of patients with bladder cancer, 75%-80% initially present with superficial bladder tumors. Treatment of these tumors has three objectives: 1) to eradicate existing disease, 2) to provide prophylaxis against tumor recurrence, and 3) to avoid deep invasion into the muscle layers of the bladder. Transurethral resection is the primary treatment to eradicate superficial bladder tumors, but 40%-80% of these tumors recur. Because of these high recurrence rates, adjuvant intravesicular pharmacotherapy with cytotoxic and immunomodulatory drugs has gained widespread use. The past two decades of clinical investigations in superficial bladder cancer have provided valuable information on the biology and treatment of the disease. Multivariate analyses have indicated that tumor grade and stage are the most important prognostic variables commonly available to the clinician to identify the patient at greatest risk of developing muscle-invasive or metastatic bladder cancer. These studies have also identified groups at low risk for tumor recurrence and invasive bladder cancer. Randomized trials have shown that recurrence rates are decreased by adjuvant intravesicular pharmacotherapy with a number of drugs: bacillus Calmette-Guérin vaccine (BCG), doxorubicin, ethoglucid (Epodyl), mitomycin-C, teniposide, and thiotepa. However, few studies indicate that adjuvant intravesicular pharmacotherapy can prevent progression to invasive bladder cancer in the high-risk patient with superficial bladder cancer. Additional clinical trials are needed to determine whether such therapy can prevent invasive and metastatic bladder cancer and improve disease-free survival in this group. In addition, the identification of tests (e.g., monoclonal antibody tests, chromosomal analyses, and tumor marker assays) that can help to identify high-risk patients is needed to better develop therapeutic strategies for superficial bladder cancer.     

Association of cyclooxygenase-2 immunoreactivity with tumor recurrence and disease progression in superficial urothelial bladder cancer

AIMS AND BACKGROUND: The main characteristic of urothelial bladder cancer is a clear predisposition to recurrence and disease progression. The aim of this study was to assess the possible relationship between cyclooxygenase-2 (COX-2) immunoreactivity in superficial urothelial bladder carcinoma and tumor grade, stage, number of recurrences and clinical disease progression. METHODS: In this prospective study 70 consecutive patients who underwent transurethral resection for superficial urothelial bladder cancer were included. Tumor slides were immunohistochemically stained for COX-2, and COX-2 immunoreactivity in tumor and inflammatory stromal cells was categorized as negative or mildly, moderately or strongly positive. Patients were followed up for 2 years, and during this period the possible association of COX-2 immunoreactivity with tumor stage and grade, number of recurrences and progression of disease was evaluated. RESULTS: COX-2 immunoreactivity in tumor cells was found in 57 (81.4%) patients and did not correlate with tumor grade, stage of disease, number of recurrences, and progression of disease. COX-2 immunoreactivity in inflammatory cells was found in 16 of the 57 patients with COX-2 positive tumors, and was significantly related to the number of recurrences, time to appearance of the first recurrence, and disease progression. CONCLUSIONS: COX-2 immunoreactivity in inflammatory stromal cells adjacent to the COX-2-positive tumor might be useful in clinical practice for selection of patients with a high risk of tumor recurrence and disease progression.     

膀胱移行细胞癌中p53突变、bcl-2和PCNA表达的临床意义(英文)

目的探讨膀胱癌中 bcl-2、p53、PCNA 表达与细胞增殖、凋亡和临床病理学参数之间的关系。方法 SABC 免疫组化分折62例(T1G1-G339例,T2-T4aG3 NOM023例)甲醛固定和石蜡包埋的膀胱癌标本 bcl-2、p53和 PCNA 蛋白的免疫反应性。平均随访37个月,24例复发。增殖指数(PI)表示肿瘤细胞中 PCNA 阳性细胞百分比。TUNEL 法检测细胞凋亡,凋亡指数(AI)表示肿瘤细胞中凋亡细胞的百分比。结果 62例膀胱癌中,50例(80.0%)发生 p53突变,与 G1(72.7%)和 G2(78.5%)相比较 G3(91.3%)更多见(P<0.05);pT2期(95.7%)p53突变率较 pTa-1期(74.3%)高(P<0.01)。14例(22.5%)发现有 bcl-2表达,bcl-2表达阳性率 G3明显高于 G1和 G2(P<0.05),与分期无关(P>0.05)。Bcl-2表达与 p53突变无关。在膀胱癌中,PI 为17.2%～41.8%(平均为22.4%),AI 为1.9%～3.5%(平均为2.9%)。统计分析显示 PI 与肿瘤分级、分期关系密切,AI 与肿瘤的分级有明显关系。结论结果表明,p53突变与浸润性行为呈正相关。在膀胱癌中 p53和 PCNA 过表达可能能提供有价值的预后信息。随着肿瘤的进展,肿瘤细胞过度增殖可能伴有频繁的凋亡,但增殖指数的增加明显强于凋亡指数的增加。     

Patterns of multiple recurrences of superficial (Ta/T1) transitional cell carcinoma of bladder and effects of clinicopathologic and biochemical factors

BACKGROUND: Although multiple sequential recurrences are one of the most important characteristics of superficial transitional cell carcinoma (TCC) of the bladder, few studies have examined multiple sequential recurrence patterns and the clinicopathologic and biochemical factors associated with these patterns. METHODS: Two hundred seventy superficial TCC bladder carcinoma patients were followed. Clinical, pathologic, and tumor marker (p53, MIB-1, bcl-2, c-erb B-2, and epidermal growth factor receptor) data were collected at baseline and during followup. The Kaplan-Meier (KM) method was used to describe multiple recurrences. The Wei, Lin, and Weissfeld (WLW) marginal proportional hazards model was used to assess the effects of clinicopathologic and immunohistochemic factors on multiple recurrences. RESULTS: Among the 270 patients, 126 (46.7%) had one or more recurrences, 38 (14.1%) had two or more recurrences, and 14 (5.2%) had three or more recurrences during the followup. The median times for the first, the second, and the third recurrences were 23 months, 15 months, and 13 months, respectively. In KM analysis, Stage T1, higher grades, and Ki-67 stain positivity were associated with the first recurrence, and p53 stain positivity was marginally significant. Other markers were not significant. For the second recurrence, only p53 stain positivity was significant. In multivariate analysis (WLW method), stage was significantly associated with the first recurrence (risk ratio [RR] = 2.03), and Ki-67 was marginally significant (RR = 1.49). For the second recurrence, only p53 positivity was statistically significant (RR = 2.73). CONCLUSIONS: Among superficial TCC bladder carcinoma patients, multiple recurrences are common phenomena. The time for recurrence becomes shorter as the number of recurrences increases. In addition to tumor stage and grade, Ki-67 can be used to identify patients at high risk for a first recurrence; and p53 can be used to identify patients at high risk for a second recurrence.     

Bladder carcinoma in patients age 40 years or younger

The records of 26 men and nine women aged 40 years or younger, with transitional cell carcinoma of the bladder, were reviewed. Twenty-eight of the patients presented with gross painless hematuria, and 30 were regular smokers. Twenty-two patients presented with noninvasive disease, five with superficial invasion and eight with deep invasion. The risk of the disease progressing to invasion increased with the grade of the tumor, rising from 24% with Grade 1 to 75% with Grade 3. The patients younger than 30 years presented with a lower grade and a lower stage disease than those older than age 30. Transitional cell carcinoma of the bladder in young adults has a natural history similar to that seen in older patients.     

Age as a predictor of an aggressive clinical course for superficial bladder cancer in men.

Tumor grade and stage are two of the strongest predictors for indolent versus aggressive clinical course in bladder cancer. To identify age-related trends in tumor aggressiveness the authors investigated the relationships of age with grade and stage. Pathologic specimens were obtained for 89% (527 of 590) of new bladder cancer cases among men older than 50 years of age reported to the state tumor registry in Wisconsin for 1988. Tumors were grouped as low grade (G1, G2) or high grade (G3), and as superficial (Ta) or invasive (greater than or equal to T1), according to the TNM system. This analysis included 485 transitional cell carcinomas (TCC) for which the authors determined stage-stratified and grade-stratified odds ratios for men 50 through 64 years of age and older than 65 years of age. Men older than 65 years of age with superficial TCC were more than three times as likely to have a high-grade malignancy than men 50 through 64 years of age (P = 0.01); the odds ratio was 3.44 (95% CI = 1.28, 9.26). A relationship was not apparent for invasive TCC. Age and stage were weakly associated for low-grade and high-grade TCC that may be due, in part, to the strong correlation of stage with grade as a prognostic indicator. These data suggest that men in older age groups are at increased risk for superficial bladder cancer of high grade, which portends an aggressive clinical course.     

Predictive value of expression of transforming growth factor-beta(1) and its receptors in transitional cell carcinoma of the urinary bladder.

BACKGROUND: The purpose of this study was to describe the expression patterns of transforming growth factor (TGF)-beta(1) and its receptors in transitional cell carcinoma (TCC) of the bladder, to investigate the relation between the TGF-beta(1) and its receptors, and to determine whether altered expression of TGF-beta or its receptors is associated with disease progression and survival in patients with TCC of the bladder. METHODS: Immunohistochemical staining for TGF-beta(1) and its receptors I and II was conducted on formalin fixed paraffin embedded archival cystectomy specimens of 80 patients with bladder TCC. Immunoreactivity was categorized as either positive or negative in a blinded fashion. RESULTS: Expression of TGF-beta(1), TGF-beta-RI, and TGF-beta-RII was altered in 51 (64%), 34 (43%), and 38 (48%) specimens, respectively. Sixty (75%) specimens had altered expression of at least 1 of the 3 TGF-betas, and 26 (33%) had altered expression of all 3. Expression of the three TGF-betas was highly concordant (P < 0.018). Loss of expression of TGF-beta-RI or TGF-beta-RII was associated with invasive tumor stage (P < 0.001), high grade (P < 0.006), and lymphovascular invasion (P < 0.030). Overexpression of TGF-beta(1) was associated with invasive tumor stage only (P = 0.024). With a median follow-up of 101 months, TGF-beta-RI was an independent predictor of both disease progression (P = 0.007) and disease specific survival (P = 0.006) whereas TGF-beta(1) was an independent predictor of disease progression only (P = 0.050). Transforming growth factor-beta-RII was not independently associated with either disease progression or survival. CONCLUSIONS: Altered expression of TGF-beta(1) and its receptors is common in TCC of the bladder. Overexpression of TGF-beta(1) is associated with the loss of expression of its receptors. Transforming growth factor-beta(1) and TGF-beta-RI are independently associated with clinical outcome in patients with bladder TCC treated by radical cystectomy.     

Thymidine phosphorylase expression as a prognostic marker for predicting recurrence in primary superficial bladder cancer

No prognostic marker for predicting recurrence in primary superficial bladder cancer has been established. The aim of this study was to investigate the expression levels of thymidine phosphorylase (TP) by enzyme-linked immunosorbent assay (ELISA) and the immunohistological localization of TP in primary superficial bladder cancer tissue to assess its association with tumor recurrence and stage progression as well as the pathological parameters of the tumor. TP expression in cancer tissues from 77 patients was measured by sandwich-type ELISA. Clinicopathological factors and the clinical prognosis were examined in relation to the expression levels of TP. To clarify the clinicopathological implication of TP localization in primary superficial bladder cancer tissue, the immunohistochemically determined TP expression was assessed for histological grades 1-3. The TP expression in primary superficial bladder cancer significantly increased with the histological grade and stage. The TP expression in patients with a shift to invasive cancer was significantly higher than in those without invasive cancer. Patients with low TP expression had a significant longer postoperative tumor-free period than those with high TP expression (P=0.011). High TP expression was an independent prognostic factor for tumor recurrence (P=0.0441). Strong immunoreactivity for TP was observed in the cytoplasms of tumor cells and vascular endothelial cells. This study suggests that elevated TP expression may be a prognostic marker for predicting recurrence in primary superficial bladder cancer, and that high TP expression may be associated with the marked proliferation of tumor cells and increased vascular endothelial cells, showing strong immunoreactivity for TP.     

Molecular genetic alterations in superficial and locally advanced human bladder cancer.

We attempted to define the role of tumor suppressor genes in the pathogenesis of human bladder cancer through a combined molecular genetic and immunohistochemical approach. Thirty-four bladder tumors (1 Pis, 6 Pa, 5 P1, 3 P3a, 18 P3b, 1 P4; 8 low grade and 26 high grade tumors) have been analyzed. Restriction fragment length polymorphism analysis directed at 5 suspected or established tumor suppressor gene regions (3p21-25, 11p15, 13q14, 17p11-13, and 18q21) was combined with immunohistochemical using Rb-PMG3-245 monoclonal antibody directed at the retinoblastoma (Rb) gene product. Tumor grade correlated with deletions of 3p (P = 0.004) and 17p (P = 0.063). Tumor stage correlated with deletions of 3p (P = 0.010), 17p (P = 0.015) and altered Rb expression (P = 0.054). Vascular invasion correlated only with deletions of 17p (P = 0.038). No marker correlated with positive lymph nodes. Our results suggest that altered Rb expression occurs in all grades and stages of bladder cancer but is more commonly associated with invasive tumors. Genetic alterations of 3p, 11p, 17p, and 18q are rare events in low grade, superficial tumors, whereas they are more common in high grade and invasive bladder cancer. The role of these genetic alterations in the prognosis of bladder cancer will require additional follow-up and further studies.     

Association of matrilysin expression with recurrence and poor prognosis in human esophageal squamous cell carcinoma.

Matrix metalloproteinase-7 (matrilysin) has been implicated in tumor invasion and metastasis as well as tumor initiation and growth. In this study, we analyzed an association between immunohistochemically detected matrilysin expression at the invasive front in esophageal squamous cell carcinomas and clinicopathological characteristics and determined whether matrilysin predicts recurrence and/or survival Matrilysin expression at the invasive front was detected in 49% of 100 carcinoma tissues and was associated with the depth of invasion (P < 0.0001), advanced tumor stage (P = 0.0159), recurrences (P = 0.0002), and recurrences within the first postoperative year (P = 0.002). Patients with matrilysin-positive carcinoma had a significantly shorter disease-free and overall survival time than did those with a matrilysin-negative one (P < 0.0001). Matrilysin remained a significant predictive value for disease-free and overall survival in multivariate analysis, including conventional clinicopathological factors (P = 0.0007 and 0.0004, respectively). Our results suggest that matrilysin may play a key role in the progression of esophageal carcinoma and that its detection may be useful for the prediction of recurrence and poor prognosis and, possibly, for selecting patients for anti-matrix metalloproteinase therapy.     

膀胱移行细胞癌中p53突变、bcl-2和PCNA表达的临床意义

To correlate the frequency of p53 mutations, bcl-2 expression and the proliferation status (proliferating cell nuclear antigen, PCNA) in patients with bladder cancer with cell proliferation, apoptosis and their clinico-pathologic findings. Paraffin-embedded sections from 39 superficial (T1G1-G3) and 23 invasive (T2-T4a G3 N0M0) primary transitional cell carcinomas (TCC) in the bladder were investigated immunohistochemically for p53, bcl-2 and PCNA. The median follow-up was 37 months; 24 had recurrences. The proliferation index (PI) was expressed as a percentage of the PCNA-positive cells in the tumor cells. Apoptosis was detected by terminal deoxy-nucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and the apoptotic index (AI) was expressed as a percentage of the TUNEL-positive tumor cells. p53 mutation was identified in 50 patients (80.6%). The mutation was most common in tumors grade 3 (91.3%) as compared to grade 2 (78.5%) and grade 1 (72.7%, P<0.05). Stage pT2 tumors had a higher frequency of p53 mutation (95.7%) as compared to pTa-1 tumors (74.3%, P<0.01). Only 14 tumors (22.5%) expressed bcl-2; grade 3 tumors expressed bcl-2 significantly more frequently (P<0.05); there was no correlation between bcl-2 and tumor stage. There was no interrelation between p53 mutation and bcl-2 expression (P>0.05). The PI ranged from 17.2% to 41.8% (median 22.4%) and the AI from 1.9% to 3.5% (median 2.9%) in bladder cancer. Statistical analyses revealed a close associations between PI, AI and tumor grade and stage of bladder cancer. p53 mutation correlates with invasion. p53 and PCNA overexpression may offer valuable additional prognostic information in bladder tumors. With the progression of the tumor grade, cell proliferation may be accompanied by frequent apoptosis in bladder cancer, but the PI increased much more than the AI.     

IMP3 predicts aggressive superficial urothelial carcinoma of the bladder

PURPOSE: In this study, we investigated whether an oncofetal protein, IMP3, can serve as a new biomarker to predict progression and metastasis of early-stage urothelial carcinoma of the bladder. EXPERIMENTAL DESIGN: The expression of IMP3 in 242 patients with primary superficial bladder urothelial carcinoma and metastatic urothelial carcinoma was evaluated by immunohistochemistry. Patients with primary superficial urothelial carcinoma of the bladder were further investigated by use of survival analysis. RESULTS: Twenty percent (42 of 214) of primary superficial urothelial carcinomas and 93% (26 of 28) of metastatic urothelial carcinomas expressed IMP3. Kaplan-Meier plots and log-rank tests showed that patients with IMP3-positive tumors had a much lower progression-free survival (P = 0.0002) and disease-free survival rate (P = 0.0067) than did those with IMP3-negative tumors. The 5-year progression-free and disease-free survival rates were 91% and 94% in IMP3-negative patients versus 64% and 76% in IMP3-positive patients, respectively. Sixty percent of IMP3-positive patients with superficial invasive urothelial carcinoma at initial diagnosis went on to develop metastases, whereas no metastasis was found in IMP3-negative patients (P = 0.0017). In the multivariable Cox analysis, patients with IMP3 expression in their superficial urothelial carcinomas subsequently developed invasive tumors or metastasis at a rate that was about five times greater than cases without expression of IMP3 adjusting for other well-known clinical variables (tumor stage and grade, etc.). CONCLUSIONS: Our findings indicate that IMP3 is an independent prognostic marker that can identify a group of patients with a high potential to develop progression and who might benefit from early aggressive therapy.     

Superficial bladder cancer.

The majority of patients with bladder cancer have superficial disease. Occupational exposure to metabolites of aniline dyes and other aromatic amines has been associated with the development of bladder cancer. Latency periods can reach 50 years. Cigarette smoking has also been strongly linked to bladder cancer as an etiologic factor. The diagnosis of superficial bladder cancer can be elusive because its symptoms mimic those of other common urologic conditions such as urinary tract infection and prostatism. A high index of suspicion is required and a search for bladder cancer should be initiated in any adult (especially those over 50 years of age) who exhibits asymptomatic gross or microscopic hematuria, or irritative voiding symptoms. Cystoscopy is required for the screening and diagnosis of superficial bladder cancer, and resection of the lesion can be performed cystoscopically as well. Laser ablation of superficial lesions provides a treatment alternative that is less invasive and better tolerated by the patient, but it does not yield a tissue specimen for analysis. Urinary cytology has been invaluable in the screening, diagnosis, and follow-up of superficial bladder cancer patients, and now flow cytometry and image analysis techniques can complement it and may eventually supplant it. The key to the management of superficial bladder cancer is to identify those patients that may be at risk for recurrence and, more importantly, those who may progress to invasive or metastatic disease. Fortunately, most superficial bladder cancer remains superficial, and the overall prognosis is good, with 5-year survival rates for superficial disease of approximately 75%. As the natural history of superficial bladder cancer has become more evident through extensive research, risk factors such as tumor size, multiplicity, grade, depth of invasion, and condition of the surrounding mucosa have emerged. T1 lesions, those that invade the lamina propria, have a more ominous course than T0 and TA lesions. The mainstay of treatment for superficial disease is transurethral resection of the lesion or lesions. Intravesical therapy has been shown to have a definite effect in eradicating existing disease as well as reducing recurrences, but it has not been shown to prevent invasive disease.(ABSTRACT TRUNCATED AT 400 WORDS)     

膀胱移行细胞癌中p53突变、bcl-2和PCNA表达的临床意义

目的　　探讨膀胱癌中bcl-2、p53、PCNA表达与细胞增殖、凋亡和临床病理学参数之间的关系。方法　　SABC 免疫组化分折62例(T1GI —G339 例,T2-T4aG3　NOM023例)甲醛固定和石蜡包埋的膀胱癌标本bcl-2、p53 和PCNA蛋白的免疫反应性。平均随访37个月,24例复发。增殖指数(PI)表示肿瘤细胞中PCNA阳性细胞百分比。TUNEL法检测细胞凋亡,凋亡指数(AI)表示肿瘤细胞中凋亡细胞的百分比。结果　　62例膀胱癌中,50例(80.0%)发生p53突变,与G1(72.7%)和G2(78.5%)相比较G3(91.3%)更多见(P<0.05);pT2期(95.7%)p53突变率较pTa-1期(74.3%)高(P<0.叭)。14例(22.5%)发现有bel-2表达,bcl-2表达阳性率G3明显高于G1和G2(P<0.05),与分期无关(P>0.05)。Bcl-2表达与p53突变无关。在膀胱癌中,PI 为17.2%～41.8%(平均为22.4%),AI为1.9%-3.5%(平均为2.9%)。统计分析显示PI与肿瘤分级、分期关系密切,AI与肿瘤的分级有明显关系。结论　　结果表明,p53突变与浸润性行为呈正相关。在膀胱癌中p53和PCNA过表达可能能提供有价值的预后信息。随着肿瘤的进展,肿瘤细胞过度增殖可能伴有频繁的凋亡,但增殖指数的增加明显强于凋亡指数的增加。     

IASLC分级系统与Ⅰ期浸润性非黏液型肺腺癌患者预后关系的回顾性研究

目的：回顾性分析国际肺癌研究协会(IASLC)分级系统与Ⅰ期浸润性非黏液型肺腺癌临床病理特征的相关性及与患者预后的关系。方法：回顾性分析2015年1月至2018年12月就诊于天津市胸科医院的204例Ⅰ期浸润性非黏液型肺腺癌患者的临床病理资料及随访资料,根据IASLC分级系统对患者分组,采用单因素方差分析、χ²检验和Fisher精确检验分析IASLC分级与Ⅰ期浸润性非黏液型肺腺癌临床病理特征的相关性,及与肺腺癌患者预后的关系。通过Kaplan-Meier法计算浸润性非黏液型肺腺癌患者总生存率(overall survival,OS)、无复发生存率(recurrence-free survival,RFS);采用Log-rank法比较不同组间的差异性。使用单因素Cox回归、多因素Cox回归分析独立危险因素。结果：204例患者中IASLC分级为Ⅰ级108例,Ⅱ级66例,Ⅲ级30例。IASLC分级与性别(P=0.022)、吸烟史(P=0.041)、脉管侵犯(P=0.004)、胸膜累及(P=0.001)、病理分期(P<0.001)、肿瘤直径(P<0.001)均显...     

Clinical significance of human erythrocyte glucose transporter 1 expression at the deepest invasive site of advanced colorectal carcinoma

OBJECTIVE: Malignant cells exhibit increased glucose uptake and utilization in vitro and in vivo. This process is thought to be mediated by the glucose transporter (Glut) family. The aim of this study was to elucidate the clinical significance of Glut1 expression at the site of deepest invasion as a predictor of the invasive/metastatic potential and prognosis of advanced colorectal carcinoma (CRC). METHODS: One hundred and fifty-two patients who had undergone surgical resection for advanced CRC were entered in this study. Histologic subclassifications at the deepest invasive site included well-differentiated (W), moderately to well-differentiated (Mw), moderately to poorly differentiated (Mp), poorly differentiated (Por) and mucinous (Muc) adenocarcinomas. Glut1 expression was examined immunohistochemically with a labeled streptavidin-biotin kit using anti-Glut1 polyclonal antibody MYM. As a marker of cell proliferation, Ki-67 expression was also examined. All immunoreactivity was analyzed at the deepest invasive site, central portion and superficial part. The immunohistochemical expression of Glut1 was defined as positive if distinct staining of the membrane or cytoplasm was observed in at least 30% of tumor cells. RESULTS: Glut1 expression was detected in 56 of 152 lesions (36.8%) at the deepest invasive site. The incidence of Glut1 expression at the deepest invasive site correlated significantly with histologic grade (W/Mw grade, 28% vs. Mp/Por/Muc grade, 48%), depth of invasion (invasion of muscularis propria/invasion of subserosa or subadventitia, 29% vs. invasion of serosa or adventitia/invasion of adjacent structures, 52%), lymphatic invasion (absence of lymphatic invasion, 19% vs. presence of lymphatic invasion, 40%), lymph node metastasis (absence of lymph node metastasis, 25% vs. presence of lymph node metastasis, 41%) and Duke's stage (Duke's 相似文献