Predictive and prognostic markers in a series of patients with head and neck squamous cell invasive carcinoma treated with concurrent chemoradiation therapy.
Predictive and prognostic markers in a series of patients with head and neck squamous cell invasive carcinoma treated with concurrent chemoradiation therapy.
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一系列同步放化疗治疗的头颈部鳞状细胞浸润性癌患者的预测和预后标志物。
DOI：
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发表时间：
1995
影响因子：
11.5
通讯作者：
F. Pezzella
中科院分区：
文献类型：
--
作者：
G. Gasparini;P. Bevilacqua;E. Bonoldi;A. Testolin;A. Galassi;P. Verderio;P. Boracchi;R. B. Guglielmi;F. Pezzella
已有研究提出，多种抗癌药物和放射治疗可诱导以细胞凋亡为特征的细胞死亡模式。由于细胞凋亡受多个癌基因的控制，我们分析了原癌基因bcl2和p53编码的蛋白的表达。此外，我们用免疫细胞化学方法研究了细胞增殖[用PC-10单抗抗增殖细胞核抗原(PCNA)]和血管形成[用CD-31单抗和计数瘤内微血管密度(IMD)]。采用同步放化疗(顺铂80 mg/m2，卡铂375 mg/m2，每3周3次，总剂量，6~8周)治疗临床II~IV期头颈部浸润性癌(H&N)。我们将治疗前测定的这些标记物的表达与治疗反应和预后联系起来。BCL-2蛋白在37.4%的癌组织中表达(25/67可评价)，且与所研究的任何其他特征均无显著相关性。40(56.在71例可评价为P53阳性的癌中，P53阳性率为4%，热点微血管密度的中位数为38条/视野(范围18-80)，PC-10单抗标记的核的中位数百分比为50%(范围0-95%)。在单因素分析中，区域淋巴结阴性(P=0.016)、良好状态(PS=90；P=0.044)、bcl2阳性(P=0.070)和低血管形成(P=0。085)与完全缓解的可能性显著相关。在多因素分析(最终模型)中，只有IMD(连续变量，P=0.045)和PS(P=0.017)保留了统计学意义。单因素分析显示，组织学分级低(1~2级，P=0.006.0 5)、P53阴性(P=0.0 9)、bcl2阳性(P=0.0 8)、增殖细胞核抗原高表达(P=0.0 6)的患者无病生存率明显提高。在多因素分析中，仅分级(P=0.003.0 5)和P53(P=0.0 4)对无瘤生存率有意义。在单因素分析中，当仅考虑进展性死亡时，以下指标对预后有显著影响：治疗反应(P=0.00001)、PS(P=0.04)、淋巴结状态(P=0.028)、增殖细胞核抗原(P=0.04)、p53(P=0)。08)和分级(P=0.01)。在多因素分析中，只有完全缓解(P=0.00002)、高增殖细胞核抗原水平(P=0.002)和低组织学分级(P=0.002)的患者具有较好的总体生存概率。我们的结果表明，在这一系列H&N癌症患者中，一旦获得缓解，能够预测治疗反应的标志物与与预后相关的标志物是不同的。这一信息可能对临床医生开发一种更合理的H&N癌患者的治疗方法有潜在的帮助，这些患者有资格同时接受化疗和放射治疗。
It has been proposed that diverse anticancer drugs and radiation therapy may induce a mode of cell death with the characteristics of apoptosis. Since apoptosis is under the control of several oncogenes, we analyzed the expression of the protein encoded by the proto-oncogenes bcl-2 and p53. Furthermore, we studied cell proliferation [using PC-10 mAb to proliferating cell nuclear antigen (PCNA)] and vascularization [using the CD-31 mAb and by counting intratumoral microvessel density (IMD)] using immunocytochemistry. A series of 73 patients with clinical stage II-IV squamous cell invasive carcinoma of the head and neck (H&N) were treated with concurrent chemoradiation therapy (cisplatin, 80 mg/m2, versus carboplatin, 375 mg/m2, three times every 3 weeks and a total dose of radiation therapy of 64 Gy in 6-8 weeks). We correlated the expression of these markers, determined prior to treatment, with response to the therapy and prognosis. Bcl-2 protein was expressed in 37.4% of the carcinomas (25/67 evaluable), and it was not significantly associated with any other feature studied. Forty (56. 4%) of the 71 carcinomas evaluable for p53 were p53 positive; the median IMD was 38 microvessels/field at the hot spot (range, 18-80), and the median percentage of nuclei labeled by the PC-10 mAb was 50% (range, 0-95%). In the univariate analysis, regional lymph node negativity (P = 0.016), good performance status (PS) (PS >/= 90; P = 0.044), bcl-2 positivity (P = 0.070), and low vascularization (P = 0. 085) were significantly associated with a higher probability of complete remission. In the multivariate analysis (final model), only IMD (continuous variable; P = 0.045) and PS (P = 0.017) retained significance. As far as prognosis is concerned, in the univariate analysis, patients with tumors with low histological grading (grades 1-2; P = 0.006), p53 negative (P = 0.09), bcl-2 positive (P = 0.08), and high PCNA labeling (P = 0.06) had a significantly better disease-free survival. In the multivariate analysis, only grading (P = 0.003) and p53 (P = 0.04) retained significance for disease-free survival. For overall survival, in the univariate analysis, the following markers were significantly prognostic when only deaths due to progression are considered: response to therapy (P = 0.00001), PS (P = 0.04), nodal status (P = 0.028), PCNA (P = 0.04), p53 (P = 0. 08), and grading (P = 0.01). In the multivariate analysis, only patients who achieved complete response (P = 0.00002), high PCNA values (P = 0.002), and low histological grading (P = 0.01) retained a statistically significant probability of better overall survival. Our results suggest that in this series of H&N cancer patients the markers capable of predicting response to therapy are distinct from those associated with prognosis, once the remission has been achieved. This information is potentially useful to the clinician for developing a more rational therapeutic approach for H&N cancer patients eligible for concurrent chemoradiation therapy.
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成纤维细胞生长因子 4 增强电离辐射后 G2 期停滞和细胞存活率。
影响因子：
11.2
作者：
Jung,M;Kern,FG;Jorgensen,TJ;McLeskey,SW;Blair,OC;Dritschilo,A
通讯作者：
Dritschilo,A
影响因子：
11.2
作者：
A. Haimovitz-Friedman;Naomi Balaban;M. McLoughlin;Desiree Ehleiter;Joseph Michaeli;Israel Vlodavsky;Zvi Fuks
通讯作者：
A. Haimovitz-Friedman;Naomi Balaban;M. McLoughlin;Desiree Ehleiter;Joseph Michaeli;Israel Vlodavsky;Zvi Fuks
影响因子：
8
作者：
B. Vanhaesebroeck;John Calvin Reed;D. De Valck;J. Grooten;T. Miyashita;S. Tanaka;R. Beyaert;F. van Roy;W. Fiers
通讯作者：
B. Vanhaesebroeck;John Calvin Reed;D. De Valck;J. Grooten;T. Miyashita;S. Tanaka;R. Beyaert;F. van Roy;W. Fiers
影响因子：
158.5
作者：
WEIDNER, N;SEMPLE, JP;FOLKMAN, J
通讯作者：
FOLKMAN, J
DOI：
--
发表时间：
1988-10
期刊：
The American journal of pathology
影响因子：
--
作者：
H. Dvorak;J. Nagy;J. Dvorak;A. Dvorak
通讯作者：
H. Dvorak;J. Nagy;J. Dvorak;A. Dvorak