喉癌P53蛋白表达的临床意义

以免疫组化方法，用单克隆抗体ＤＯ－７检测了３８例喉鳞癌和２９例喉部良性病变组织中的突变型Ｐ５３蛋白的表达情况。结果显示：①６６％（２５／３８）的喉鳞癌中检出突变型Ｐ５３蛋白，喉良性病突变型Ｐ５３蛋白的阳性率仅为７％（２／２９）。突变型Ｐ５３蛋白在喉癌中的高比率表达与喉癌的的发生有关。以该蛋白是否表达作为喉癌的诊断和鉴别诊断的辅助依据，具有一定价值。②在部分喉鳞癌的癌旁呈不典型增生的上皮中，也可见突     

喉癌肿瘤标志物和喉癌分子切缘及临床因素与喉癌复发的相关性研究

目的:从喉癌肿瘤标志物、喉癌分子切缘以及临床因素三个方面分析喉癌复发的相关因素.方法:应用免疫组织化学方法检测喉癌复发组与未复发组原发灶、喉癌外科切缘的CyclinD1、p27、p53以及eIF4E表达状况,通过回顾性分析103例喉癌的临床资料,探讨喉癌复发的临床因素;并综合三方面因素对喉癌复发进行多因素分析.结果:喉癌术后复发组与未复发组原发灶的CyclinD1、p27、p53表达差异均有统计学意义(均P<0.05),eIF4E表达差异无统计学意义(P>0.05).两组切缘的CyclinD1、p27、p53、eIF4E表达差异均有统计学意义(均P<0.05),喉癌复发组eIF4E切缘阳性表达率高于CyclinD1、p27和p53.喉癌术后复发与原发肿瘤部位、T分期、淋巴结转移、喉癌病理分化程度以及首次手术方式有关;与年龄、性别、是否术后放疗无关.Logitic多因素回归分析显示:喉癌术后复发与肿瘤T分期、淋巴结转移、喉癌病理分化程度以及首次手术方式有关.综合肿瘤标志物、喉癌分子切缘以及临床因素三个方面的Logistic多因素回归分析显示:喉癌术后复发与喉癌T分期、颈部淋巴结转移、病理分化程度以及分子切缘阳性有关.结论:影响喉癌术后复发的因素复杂多样;喉癌T分期高、有颈部淋巴结转移、病理分化程度差以及分子切缘阳性者术后容易复发;喉癌分子切缘阳性是更为敏感的喉癌复发因素.     

Survivin在喉鳞状细胞癌手术切缘中的表达及与预后的关系

目的:探讨Survivin在喉鳞状细胞癌(LSCC)手术切缘中的表达情况及与肿瘤局部复发和5年生存率的关系。方法:选择常规病理学检查手术切缘为阴性的LSCC患者54例,应用免疫组织化学技术(SP法)和图像分析技术,定量检测切缘与原发灶中Survivin的表达,并结合随访资料进行分析。结果:①Survivin在原发灶中66.7%(36/54)阳性表达,手术切缘中40.7%(22/54)阳性表达,在对照组的20例中,Survivin表达均阴性。原发灶、手术切缘及对照组间的阳性指数(positiveindex,PI)差异均有统计学意义(均P<0.01)。②局部复发组手术切缘SurvivinPI(92.7±10.3)显著高于无局部复发组(52.4±16.7),差异有统计学意义(P<0.01)。③手术切缘Survivin阳性组与阴性组的5年生存率分别为29.3%和58.5%,差异有统计学意义(P<0.01)。结论:手术切缘Survivin表达阳性在一定程度上提示喉癌术后局部复发的可能和预后较差,可望指导术后辅助治疗。     

p53蛋白在喉鳞癌及癌旁组织中表达的研究

应用抗ｐ５３单克隆抗休琢ＬＳＡＢ免疫组织化学染色法检测喉鳞癌，喉癌旁组织及声带息肉ｐ５３蛋白的表达。结果显示：２５例喉鳞癌呈阳性反应，４例距肿瘤边缘〈０．５ｃｍ的喉癌旁组织呈弱阳以应，２０例距肿瘤边缘〉２ｃｍ的喉癌旁组织及１６例声带息肉均为阴性。     

P53蛋白在喉白斑及喉癌组织中的表达及其临床意义(摘要)

本研究采用免疫组织化学技术检测Ｐ５３蛋白在声带息肉、喉白斑和喉癌组织中的表达，探讨喉上皮从正常状态向恶性转化的过程中，Ｐ５３蛋白表达规律及其可能的作用机制，以期为临床病理诊断和预后评估提供依据。选用我院１９９２年至１９９９年喉活检或手术标本5８例，其中声带息肉１２例，喉粘膜白斑３０例，喉癌１６例，其中原位癌１例，高分化１１例，低分化４例。组织块用１０％福尔马林缓冲液固定，常规石蜡包埋、制片，所有患者术前均示未经放疗和化疗。应免疫组化方法测Ｐ５３表达情况。结果：Ｐ５３蛋白阳性显色为棕色，呈弥漫性或…     

喉癌微血管生成中P53nm23蛋白和血管内皮生长因 …

目的 探讨Ｐ５３、ｎｍ２３蛋白和血管内皮生长因子（ｖａｓｃｕｌａｒ ｅｎｄｏｔｈｅｌｉａｌ ｇｒｏｗｔｈ ｆａｃｏｒ,ＶＥＧＦ）在喉癌微血管生成及转移中的作用。方法 通过免疫组化ＳＰ法对４２例喉癌标本中Ｐ５３、ｎｍ２３蛋白、ＶＥＧＦ及微血管密度（ｍｉｃｒｏｖｅｓｓｅｌ ｄｅｎｓｉｔｙ,ＭＶＤ）进行了检测。结果 喉癌中Ｐ５３、ｎｍ２３蛋白及ＶＥＧＦ的阳性表达率分别占４７．６％、５７１％和７１．４％。     

喉鳞状细胞癌手术切缘分子水平亚健康与预后关系研究

目的：从分子水平判定喉鳞状细胞癌（LSCC）切除范围的彻底性及与预后的关系。方法：用免疫组织化学方法检测23例LSCC患者手术切缘组织中癌基因EGFR和抑癌基因p53、p27以及与凋亡有关的Bcl-2蛋白的表达情况，并通过随访观察其与肿瘤复发的关系。结果：23例LSCC患者中20例手术切缘组织细胞病理检测为阴性，其中p53阳性3例（15％），p27阳性11例（55％），Bcl-2阳性7例（35％），EGFR阳性3例（15％）。有4例肿瘤局部复发，其p27均为阴性；2例Bcl-2阳性；p53和EGFR均为阴性。结论：用免疫组织化学方法检测LSCC手术切缘EGFR、p53、p27、Bcl-2水平来判断手术范围是可行的，其中p27蛋白表达较为重要，但应同时检测多种基因。     

P＿（53）蛋白及增殖细胞核抗原（PCNA）在喉癌细胞中的表达及意义

采用ＡＢＣ免疫组化法对７８例喉癌行回顾性及前瞻性研究，测定喉癌细胞Ｐ５３蛋白及增殖细胞核抗原（ＰＣＮＡ）的表达，结合临床病理及随访资料对Ｐ５３蛋白过度表达在喉癌发生发展中的作用及意义进行探讨。结果发现，７８例喉癌中３５例（４４．９％）Ｐ５３蛋白呈过度表达，并同时存在不同程度的ＰＣＮＡ表达，且两者显著相关；Ｐ５３蛋白过度表达与临床分期相关，Ｐ５３蛋白阳性患者多处于临床较晚期；多因素回归分析表明Ｐ５３蛋白表达及临床分期是明显影响预后的独立指标，Ｐ５３蛋白阳性或临床晚期者术后３年生存率显著降低。     

抑癌基因P16在喉癌中的表达及临床意义

目的 为了解P16与喉癌发生、发展及预后的关系。方法 采用免疫组化LSAB法，检测了83例喉癌和20例喉粘膜慢性炎症组织中P16蛋白的表达情况。结果 P16蛋白在喉粘膜慢性炎症标本中表达率（100％），明显高于喉癌中的阳性表达率（65％），P＜0．01。同时P16蛋白阳性率与喉癌的临床分期、肿瘤的局部浸润程度、颈淋巴结转移率负相关程度较高，P＜0．05。但与癌组织分化程度相关不明显。结论 P16表达程度与喉癌的发生、发展过程有关，可作为了解喉癌生物学特性及判断其预后的有价值的指标。     

喉癌p53蛋白和EGFR的免疫组织化学检测及意义

应用ＬＳＡＢ免疫组织化学染色法，对３２例原发喉鳞状细胞和８例喉正常上皮组织中的ｐ５３蛋白和表皮生长因子受体做定位和定量研究。结果表明：ｐ５３蛋白在喉癌组织中的表达位于细胞核内，ＥＧＦＲ的表达位于胞浆和核膜；喉癌组织中这二种癌基因表达的蛋白阳性率，ｐ５３为５９．４％，ＥＧＦＲ为６８．８％，ＥＧＦＲ在喉癌组织中的阳性率和强度与病理分级和临床预后显著性相关，ｐ５３在喉癌早期病例中表达的阳怀率明显增高。     

Importance of anterior commissure in recurrence of early glottic cancer after laser endoscopic resection

OBJECTIVE: To analyze the impact of anterior commissure involvement on rates of local control, recurrence, and laryngeal preservation in patients with early glottic cancer (T1a-T2 lesions, staged according to the TNM staging system) treated with laser microsurgical resection. DESIGN: Retrospective review. SETTING: A tertiary university referral center. PATIENTS: Forty-eight patients with early glottic (T1-T2a) cancer. INTERVENTION: Laser endoscopic resection of glottic cancer. MAIN OUTCOME MEASURES: Evaluation of local control and larynx preservation rates. RESULTS: Among 48 patients presenting with early glottic cancer, the anterior commissure was involved in 24 cases. The local control rate was 79% (19 cases), and the larynx preservation rate was 96% (23 cases). In the 24 cases without anterior commissure involvement, the local control rate was 96% (23 cases) and the corresponding larynx preservation rate was 100% (24 cases). The rate of local recurrence with anterior commissure involvement was 21% (5 cases) and was 4% (1 case) when this site was not compromised by the tumor. This difference was not statistically significant (P = .08). When the anterior commissure was compromised by a lesion, more surgical margins taken from the patient after the completion of surgery (additional margins) were compromised by squamous cell carcinoma (SCC) on permanent section (33% [8 cases]) compared with 0% from patients with anterior commissure involvement (P = .003), despite the fact that these margins were negative for disease on frozen section. Cases with additional margins compromised by SCC on permanent section (P = .004) and T1 lesions (P = .009) had a higher rate of recurrence. CONCLUSIONS: This study shows the tendency toward greater additional margins compromised by SCC and a higher rate of tumor recurrence in lesions with anterior commissure involvement after laser microsurgery for early glottic carcinoma. Higher recurrence rates were observed in cases with compromised additional margins and in T1 cases.     

喉癌术后局部复发与手术切缘的关系

目的 :探讨喉癌术后局部复发与手术切缘的关系。方法 :对 1991～ 1999年行手术治疗并随访满 3年以上的喉癌患者的临床资料进行回顾性分析 ,分别选取手术切缘、T分期和术后放疗等因素进行统计学分析。结果 :① 16 0例喉癌患者术后局部复发 36例 ,复发率为 2 2 .5 % ;②局部复发与肿瘤的T分期有关 ,差异有统计学意义 ;③切缘≤ 3mm组的局部复发率高于切缘 4～ 5mm组和 >5mm组 ,差异有统计学意义 ;④手术切缘≤3mm的 6 9例中 ,32例行术后放疗的局部复发率低于 37例未行放疗者 ,差异有统计学意义 ;⑤声门型喉癌 5mm的手术切缘与切缘≤ 3mm组相比 ,局部复发率较低 ,差异有统计学意义。而 5mm的手术切缘对声门上型喉癌不够安全 ,与≤ 3mm组相比 ,局部复发率相似 ,差异无统计学意义。结论 :①以 5mm作为声门型喉癌的手术切缘是相对安全的 ;②以 5mm作为声门上型喉癌的手术切缘不够安全 ,如局部条件许可 ,建议以 10mm为安全切缘 ;③对手术切缘不够者行术后放疗可降低局部复发率 ,但不主张因此而放宽对安全切缘的标准。     

术中留取切缘标本对早期喉癌患者术后治疗的指导价值

目的 探讨部分喉切除术术中切缘标本对早期喉癌患者术后治疗的指导价值。方法 研究87例术中留取手术切缘标本的早期喉癌病例T1NOMO（34例）、T2NOMO（53例）。比较切缘阴、阳性组的肿瘤复发率、生存曲线;切缘阳性给予术后放射治疗组与切缘阴性组的生存曲线;切缘阴性组给予与不给予术后放射治疗的生存曲线。结果 切缘阳性组的复发率（6／18,33．3％）较阴性组（4／69,5．8％）高（x^2＝10．64,P＝0．001）,总体生存时间短（P＝0．011）,无瘤生存时间短（P＝0．007）;切缘阳性给予后放射治疗组与阴性组的生存曲线差异有显著性（P＝0．01）,但切缘阴性组给予和不给予术后放射治疗者的生存曲线差异无显著性（P＝0．405）。结论 在早期喉癌中,切缘阳性组的预后差于阴性组,最好的方法是将肿瘤切除干净;切缘阴性者不必给予术后放射治疗。     

Prognostic significance of G1 cell-cycle inhibitors in early laryngeal cancer

BACKGROUND: Radiation therapy yields a 2-year local control rate of 80% to 90% in early laryngeal squamous cell carcinoma. However, a subset of early laryngeal cancers has a significantly higher rate of local recurrence and lower rate of overall survival. OBJECTIVE: The objective of this study was determine the prognostic significance of p53, p27, and p21 expression in patients with early laryngeal cancer. METHODS: Expression of p53, p27, and p21 proteins in pretreatment biopsies from sixty-eight patients was analyzed by using immunohistochemistry. Low (10% cells) levels of expression were measured. All patients were newly diagnosed and treated with external beam radiation. Other contributing factors were also studied, such as age, sex, race, tumor site, and stage. RESULTS: Forty (58.8%) and 28 (41.2%) lesions were staged as T1 and T2, respectively, whereas 16 (23.5%) and 52 (76.5%) were located in the supraglottis and glottis, respectively. Overexpression of p27, p53, and p21 was found in 36.7%, 60.6%, and 60% of cases, respectively. Overexpression of p27 was found to be a significant predictor of recurrence by multivariate analysis (RR 3.3, P = .017). Overexpression of p21 and/or p53 was not predictive of recurrence. No factor predicted disease specific or nonspecific overall survival. CONCLUSION: Our results indicate the significance of p27 overexpression as an indicator of recurrence in patients with early laryngeal squamous cell carcinoma.     

Ki-67 (MIB1), p53, and Lewis-X (LeuM1) as prognostic factors of recurrence in T1 and T2 laryngeal carcinoma

OBJECTIVES: Recently published data suggest a prognostic value of immunohistochemical proliferation markers for limited laryngeal carcinoma. Previous studies have reported contrasting findings on this issue. In this context, different treatment modalities may be responsible for contradictory findings. To study the relationship between proliferative activity--expressed by the immunohistochemical labeling index of proliferation-associated markers Ki-67 (MIB1), Lewis-X (LeuM1), and proliferating cell nuclear antigen (PCNA) and by p53 status--and treatment failure in a matched-pair study on recurrent and nonrecurrent T1 and T2 glottic carcinoma having received primary transoral laser surgery. METHODS: Twenty-one patients with tumor recurrence were randomly selected and matched with 26 patients with nonrecurrent disease regarding histopathological grading and age. MIB1 staining was used to determine the Ki-67 labeling index, and LeuM1 staining for detecting the Lewis-X antigen; immunohistochemistry determined the p53 status and PCNA labeling index. RESULTS: The Ki-67 labeling index was significantly (P = .001) higher in tumors from patients who had treatment failure (mean = 20.02%) than in patients who did not fail treatment ("nonfailures") (mean = 9.95%). Carcinoma with a Ki-67 (MIB1) labeling index above the median (15%) of the general study population showed a mean time to relapse of 23 months (n = 21), compared with 50 months for cases (n = 26) below the median (P = .016). PCNA labeling index correlated less impressively with tumor recurrence (mean = 28.59% for treatment failures, mean = 21.75% for nonfailures, P = .022). Positive detection of the Lewis-X antigen was significantly associated with recurrence (P = .015) and time to relapse (P = .006). Status of p53 was not a significant prognostic factor. CONCLUSION: The Ki-67 (MIB1) labeling index may be associated with early relapse of limited laryngeal carcinoma treated with transoral laser surgery. Since the prognostic relevance of Ki-67 seems to be different for radiological and surgical concepts of treatment, Ki-67 might become useful as criterion of therapy selection. The Lewis-X antigen, for the first time used on laryngeal carcinoma, seems to be a strong prognostic marker deserving further investigations.     

p53在喉鳞状细胞癌及癌旁组织中的表达与生物学行为的关系及意义

目的:研究并回顾性分析喉鳞状细胞癌(LSCC)及癌旁组织中p53基因的表达及其与生物学行为的关系和意义。方法:用免疫组织化学SP法检测76例LSCC及癌旁组织中的p53表达。结果:LSCC组织中p53过表达47.4%(36/76),对应原位癌p53过表达为40.0%(4/10);癌旁非典型增生组织中p53过表达22.2%(8/36);癌旁正常组织中p53无过表达(0/56);p53在LSCC实质及相应原位癌中的表达呈现完全一致性。p53在癌旁非典型增生组织和对应癌实质组织中的过表达呈现高度显著正相关性(P<0.01);p53在癌组织中的过表达显著高于非典型增生组织(P<0.01);p53过表达和性别、年龄、临床分期、临床LSCC类型(LSCC位置)、肿瘤大小均无统计学意义,和病理分级(G1→G2 G3)有高度显著相关性(P<0.01)。p53在LSCC淋巴结转移组的过表达(68.8%)高于非转移组中的过表达(41.7%),但差异无统计学意义。LSCC病理分级(G1→G2 G3)和淋巴结转移有高度显著相关性(P<0.01)。结论:p53异常表达可出现于LSCC不同阶段及癌旁癌前病变组织中,并具有显著相关性,是LSCC发生、发展的重要因素及有意义的早期改变,并可反映喉癌组织细胞增殖活性和恶性程度及预后。     

A study of the association between local recurrence and surgical margins in vertical partial laryngectomy for T1 glottic squamous cell carcinoma

Background: The effect of surgical margins on local recurrence in T1 glottic squamous cell carcinoma (GSCC) is unclear.

Objectives: To investigate the association between surgical margins and local recurrence of T1 GSCC patients with vertical partial laryngectomy (VPL).

Materials and methods: We retrospectively studied 117 T1 GSCC patients. Close and negative margins were estimated as distance <5?mm and ≥5?mm. The effect of surgical margins on local recurrence was evaluated. For patients with invasion not reaching muscular-layer, a threshold margin of 2?mm was detected.

Results: About 109 patients were exclusively treated by VPL and 8 patients received postoperative radiotherapy. In 109 cases, the posterolateral margins and shortest margins in recurrence group were both lower than no-recurrence group (p<.01). The ratios of posterolateral margin to average diameter, upper-lower diameter and internal-external diameter in recurrence group were also statistically lower (p<.05). A threshold margin of 2?mm showed statistical difference on recurrence in patients with invasion not reaching muscular-layer.

Conclusions and significance: Posterolateral margin is crucial for local recurrence in T1 GSCC patients treated by VPL. A shortest margin of ≥5?mm should be considered. For the patients with invasion not reaching the muscular-layer, a threshold of 2?mm is enough for safe margin.     

喉鳞状细胞癌中P53和PTEN蛋白的表达及临床意义

目的 探讨喉鳞状细胞癌中P53、PTEN蛋白的表达及其与临床特征的关系。方法 采用免疫组化技术检测66例喉鳞癌组织和36例喉黏膜慢性炎症组织中P53、PTEN蛋白的表达。结果 P53、PTEN蛋白在66例喉鳞癌组织和36例喉黏膜慢性炎症组织中表达均存在统计学意义（P〈0．05）。66例喉鳞癌组织中，P53蛋白的表达水平在Ⅲ～Ⅳ期组高于Ⅰ～Ⅱ组（P〈0．05），淋巴结转移者高于无淋巴结转移者（P〈0．05）；PTEN蛋白的表达水平Ⅰ～Ⅱ期组高于Ⅲ～Ⅳ期组（P〈0．05），高分化癌组高于中低分化癌组（P〈0．05），无淋巴结转移者高于有转移者（P〈0．05）。喉鳞癌组织中P53、PTEN蛋白两者表达有相关性（P〈0．05）。结论 PTEN蛋白的表达对预测喉鳞癌的预后有一定参考价值。