非小细胞肺癌生物学特性与神经内分泌分化的关系

目的：探讨非小细胞肺癌神经内分泌（neuroendocrine,NE)分化与肺癌生物学特性的关系。方法：采用免疫组化LSAB法检测有随访资料（8年）的53例非小细胞肺癌（non small cell lung carcinoma,NSCLC)神经内分泌标志。结果：NSCLC表达NSE、S－100蛋白、chromogranin A(CgA)和synaptophysin(Syn)阳性率分别为28．3％（15／53）、66．7％（39．53）、0／53和3．8％（2／53）。NSCLC伴NE分化与瘤体分期（Tstage)、治疗后肿瘤易复发和转移相关；有淋巴结转移的NSCLC患者3年和5年生存率低。结论：部分NSCLC伴NE分化，伴NE分化的NSCLC瘤体分期高、经综合治疗后肿瘤易复发和转移。有淋巴结转移的NSCLC患者预后差。     

158例肺癌表皮生长因子受体检测及其意义探讨

目的；探讨表皮生长因子受体（ＥＧＦＲ）在肺癌中的表达特征及其临床病理意义。方法：应用ＡＢＣ免疫组织化学法对１５８例肺癌组织进行ＥＧＦＲ检测。结果：非小细胞肺 ＥＧＦＲ阳性率为８０．６％，而小细胞肺癌的ＥＧＦＲ均为阴性，并发现非小细胞肺癌ＥＧＦＲ表达与癌的组织学类型、分化程度、生物行为、肿块大小和临床分期均无相关性。结论：检测肺癌的ＥＧＦＲ有助于鉴别小细胞肺癌和非小细胞肺癌，并认为关于ＥＧＦＲ可能是     

Wnt5a和Wnt11在肺癌中的表达及意义

目的探讨Wnt5a和Wnt11在肺癌组织中的表达及与肺癌类型的关系,并评估两者表达与临床病理特征的关系。方法采用免疫组化En Vision法检测120例肺癌和20例正常肺组织中Wnt5a和Wnt11蛋白表达,并分析两者表达的相关性及与临床病理特征的关系。结果 84例非小细胞肺癌中,Wnt5a阳性率为36%,Wnt11阳性率为38%。36例小细胞肺癌中Wnt5a和Wnt11阳性率均低,分别为8.3%和0。两者在非小细胞肺癌中的表达显著高于小细胞癌。腺癌中Wnt11阳性率较高,为56%,Wnt5a为9%,鳞状细胞癌中Wnt5a阳性率较高,为50%,Wnt11为25%。两者表达与患者性别、年龄、分化程度以及淋巴结转移无明显相关性(P0.05)。结论 Wnt5a和Wnt11表达与肺癌类型有关,Wnt5a和Wnt11在非小细胞肺癌中的阳性率显著高于小细胞癌,Wnt5a在鳞状细胞癌中的表达较高,而Wnt11在腺癌中的表达较高。两者表达与肺癌患者年龄、淋巴结转移、细胞分化程度无明显相关性。     

肺癌组织p16和Rb基因mRNA表达的双重原位杂交观察

目的：研究Ｐ１６和Ｒｂ基因在ｍＲＮＡ表达及其与肺癌的关系。方法：制备ｐ１６和Ｒｂ基因ｃＤＮＡ探针,采用双重原位杂交的方法,地８９例肺癌和正常肺组织进行了Ｐ１６ 一Ｒｂ基因ｍＲＮＡ表达的定位研究。结果：小细胞肺癌ｐ１６ｍＲＮＡ阳性表达率高达８２．４％,而非小细胞肺癌阳性率为４５．８％,两者差异有显著性。非小细胞肺癌ＲｂｍＲＮＡ阳性表达率为８１．９％,而小细胞肺癌一率仅５．９％,两者差异有高度显著性,     

肺癌组织中神经风分泌细胞的临床病理意义

用ＮＳＥ和嗜铬颗粒素抗体对４０例不同类型肺癌做了免疫组化染色，以观察其与各种肺癌的分化，间质纤维组织，淋巴细胞及核分裂象的关系。４０例肺癌中鳞癌２１例，腺癌１０，小细胞癌７例，类癌２例，发现鳞癌中ＮＳＥ和嗜铬颗粒阳性率均为７６．２％，而且多分布于中－高分化，间质纤维组织多，淋巴细胞多和核分裂象少的区域。腺癌的ＮＳＥ阳性率为６０％，嗜铬颗料素阳性率为３０％，多分布于低分化区，与间质纤维组织和淋巴细胞     

卵巢粘液性肿瘤的神经内分泌分化

目的探讨卵巢粘液性肿瘤的神经内分泌分化与肿瘤分化程度、组织发生的关系。方法用免疫组织化学和免疫组织化学与组织化学联合染色方法观察７３例卵巢粘液性肿瘤（良性：３２例,交界性：２０例,恶性：２１例）病变组织中的神经内分泌细胞的形态、分布和数量。结果良性、交界性、恶性三种病变组织中ＣｇＡ和５ＨＴ的检出率分别依次为６２５％、７５０％、７６０％和３１３％、４００％、３９０％。但这些神经内分泌细胞（ＮＥＣ）的数量和分布未见明显的规律性。在４例肠型的良性肿瘤组织中见到较多ＣｇＡ阳性细胞,分布在粘液上皮的基底部,阳性率＞３０％,光镜下频繁观察到胞浆中同时含ＣｇＡ和ＰＡＳ两种阳性颗粒的中间型细胞。结论卵巢粘液性肿瘤随分化程度下降,神经内分泌细胞的检出率逐渐增加。４例肠型的良性肿瘤组织中频繁观察到胞浆中同时含ＣｇＡ和ＰＡＳ两种阳性颗粒的中间型细胞,提示这些肿瘤可能起源于具有多方向分化能力的干细胞,它们与卵巢粘液性肿瘤伴神经内分泌分化之间的确切关系,尚待研究。     

β连环素和表皮生长因子受体在非小细胞肺癌中表达的临床研究

目的:探讨β连环素和表皮生长因子受体在非小细胞肺癌中的表达及其临床意义。方法:采用免疫组化法回顾性研究了58例非小细胞肺癌标本β-catenin和EGFR的表达,并分析其表达与病理类型、分化程度和淋巴结转移的关系。结果:58例肺癌标本中β-catenin强阳性表达23例（36.66％）;EGFR强阳性表达27例（46.55％）,弱阳性表达19例（32.76％）;β-catenin和EGFR的表达与病理类型均无关;β-catenin的表达与分化程度有关;β-catenin和EGFR的表达均与有无淋巴结转移密切相关;β-catenin与EGFR的表达呈负相关关系（r=-0.3317,P=0.0110）。结论:β-catenin与EGFR的表达与非小细胞肺癌的生长分化、淋巴转移等恶性行为密切相关,EGFR的高表达可能与β-catenin表达水平降低有关。     

肺癌中EB病毒的原位杂交检测

为观察EB病毒在肺癌组织中的分布并探讨EB病毒感染与肺癌的关系，对87例肺癌组织中经多聚酶链反应（PCR）检测52例EB病毒阳性的石蜡包埋组织，用原位杂交技术进行定位检测。癌组织及癌旁肺组织原位杂交EB病毒阳性率分别为37．9％（33／87）和11．5％（IO／87）；中、低分化癌与高分化癌EB病毒阳性率有显著差异，强阳性病例均为分化较差的肿瘤；累及胸膜、肋骨、隔肌的肺癌，其EB病毒阳性率明显高于未侵及者；随着EB病毒感染的加重，淋巴细胞浸润增多。结果表明：EB病毒感染与肺癌细胞的生物学特性及肺癌的发展有关。     

肺癌组织神经内分泌分化的免疫组化研究

目的 了解非小细胞肺癌（ＮＳＣＬＣ）的神经内分泌（ＮＥ）分化特征。方法 采用ＳＰ超敏免疫组化法对１２０例ＮＳＣＬＣ和２４例ＳＣＬＣ进行了神经烯醇化酶（ＮＳＥ）、嗜铬粒素Ａ（ＣｇＡ）和突触素（ＳＹＮ）的检测。并与各型肺癌的分型及分化程度地行了相关分析。结果 三种神经内分泌标记物均为胞浆当色。ＮＳＥ和ＳＹＮ的阳性染色部分为弥漫性,部分为灶性分布。而ＣｇＡ均为小灶性分布。在ＮＳＣＬＣ中ＣｇＡ和ＳＹＮ阳性的病例ＮＳＥ均阳性,除２例外ＣｇＡ阳性的ＳＹＮ均阳性。ＮＳＥ的阳性染色除分布癌细胞外,部分间料可见非特异染色。在１２０例ＮＳＣＬＣ中,５２．５％表达ＮＳＥ,９．２％表达ＣｇＡ,２８．３％表达ＳＹＮ。在ＳＣＬＣ中１００％表达ＮＳＥ,３３．３％表达ＣｇＡ,５４．２％表达ＳＹＮ。三种标记物的阳性率与ＮＳＣＬＣ的分型及分化程度     

原发性肺癌的神经内分泌分化及临床意义

选择32例放疗、化疗后具有完整随访资料的肺癌患者,对其支气管镜活检标本应用,神经特异性烯醇化酶(NSE)、铬粒素A(CGH-A)、癌胚抗原(CEA)、角蛋白(K)进行免疫组化ABC法染色。结果,小细胞肺癌(SCLC)NSE和(或)CGH-A阳性率(6/14)44.4％。阳性者中位生存时间(21月)长于阴性者(12月),非小细胞肺癌中(NSCLC)中亦有2/18例NSE阳性,其生存时间短于阴性者中位生存时间,两类型肺癌CEA阳性及阴性者缓解率与中位生存均无明显差异。结论:(1)各类型肺癌均有NE分化。(2)具有神经内分泌分化(尤其CGH-A阳性)的SCLC患者存活时间长,临床预后较好,而NSE阳性的NSCIC较阴性者生存时间短、预后差。(3)CEA对肺癌患者的临床预后判断无明显意义。     

An ultrastructural classification of carcinomas of the lung]

For the purpose of providing more accurate histological typing of lung carcinoma, it is necessary to classify carcinomas of the lung by electron microscopy. One hundred and fifty cases of resected lung carcinoma were examined under electron microscope. The results of ultrastructural typing of lung carcinoma were as follows: 1. carcinomas showed differentiated features of glandular and squamous epithelium, including squamous cell carcinoma (28 cases), adenocarcinoma (35 cases), and adenosquamous carcinoma (29 cases). Among them, some cases were associated with neuroendocrine differentiation. In addition, solid mucinous cell carcinoma (4 cases) and adenoid cystic carcinoma (2 cases) were seen. 2. Carcinomas showed differentiated features of bronchioloalveolar epithelium, subdividing into clara cell (9 cases), type II pneumocyte (3 cases), mucinous cell (5 cases) and mixed type (4 cases). 3. Carcinomas showed differentiated features of neuroendocrine cell (Kulchitsky cell), including well differentiated (carcinoid, 13 cases), intermediately differentiated (atypical carcinoid, 12 cases), and poorly differentiated (small cell carcinoma, 6 cases). Among them, some cases were associated with squamous differentiation. The ultrastructural classification was compared with histological classification of lung carcinomas and the differences between them are discussed.     

Selective expression of trophoblastic hormones by lung carcinoma: neurendocrine tumors exclusively produce human chorionic gonadotropin alpha-subunit (hCGalpha)

Recent findings suggest that glycoprotein- and protein hormones act as local auto/paracrine growth/differentiation factors in normal and malignant tissue. An imbalanced or even selective production of human chorionic gonadotropin-alpha (hCGalpha) by neuroendocrine tumors in various organs has been reported. In this context, the ectopic production of trophoblastic hormones by lung carcinoma has not been investigated systemically. Because the determination of serum levels of hCGalpha are flawed by a number of factors, we designed an immunohistochemical study to precisely assess the comprehensive paraneoplastic auto-/paracrine hormone production by lung carcinoma of various histological types. To this end, 90 patients with primary lung neoplasms (40 neuroendocrine tumors, 29 adenocarcinomas, 20 squamous cell carcinomas, and 1 adenosquamous carcinoma) were analyzed by our well characterized monoclonal antibodies (mabs) against the glycoprotein hormones hCG, and its derivatives hCGalpha, hCGbeta, hCGbeta core-fragment (hCGbetacf), luteinizing hormone (LH, LHbeta), follicle-stimulating hormone (FSH, FSHbeta), and the protein hormones placental lactogen (PL) and growth hormone (GH). Overall, trophoblastic hormone immunoreactivity was found in 31% (28/90) of all lung carcinomas, regardless of histological differentiation. Detailed analysis showed 23% (21/90) hCGalpha-, 7% (6/90) hCGbeta, and 2% (2/90) hCGbetacf-positive cases. The tumors produced neither the intact heterodimer hCG, nor the other placental protein hormones PL-A/B and GH-V, or the hCG-related pituitary gonadotropins FSH/FSHbeta and LH/LHbeta. With regard to histological differentiation, it appeared that neuroendocrine tumors exclusively produced free hCGalpha in a distinct expression pattern depending on histological tumor grade. Thirty-eight percent (15/40) of all neuroendocrine neoplasms were hCGalpha-positive, and marker positivity increased with more mature, highly differentiated tumors (20% of small cell neuroendocrine carcinomas versus 90% of atypical and typical carcinoids). This is in striking contrast not only to trophoblastic malignancies and testicular germ cell tumors, but also to nontrophoblastic tumors, such as gynecological and urothelial malignancies, 60% of which produce hCGbeta and where marker positivity correlates with poor histological tumor differentiation. In conclusion, free hCGalpha, but not hCGbeta, is a useful marker for neuroendocrine differentiation in primary lung tumors. The fact that it is preferentially produced by the differentiated tumor types (carcinoids) points to a putative biological function in these tissues. The few hCGbeta-positive NSCLC must not be confounded with primary mediastinal choriocarcinoma.     

Immunoreactivity for epithelial and neuroendocrine antibodies are useful in the differential diagnosis of lung carcinomas

The histologic classification of pulmonary neoplasms can have important implications regarding appropriate management of patients. Although the histologic classification of lung tumors is predominantly based on morphology, ancillary studies such as immunohistochemistry can be used in difficult cases, and the diagnosis of large cell neuroendocrine carcinoma requires confirmation of neuroendocrine differentiation by immunohistochemistry or electron microscopy. We immunostained 142 lung tumors for B72.3, keratin 34betaE12, keratin 7, keratin 14, keratin 17, synaptophysin, and chromogranin to determine the utility of neuroendocrine markers and epithelial markers in the differential diagnosis. Among neuroendocrine carcinomas (small cell carcinoma and large cell neuroendocrine carcinoma), 84% (37 of 44) were chromogranin positive, 64% (21 of 36 small cell, 6 of 6 large cell neuroendocrine) were synaptophysin positive, 5% (2 of 43) were keratin 34betaE12 positive, 9% (4 of 44) were keratin 7 positive, and 5% (2 of 37) of small cell carcinomas and 50% (3 of 6) of large cell neuroendocrine carcinomas were B72.3 positive. Among non-neuroendocrine carcinomas, 5% (5 of 98) were chromogranin positive, 3% (3 of 96) were synaptophysin positive, and 97% (95 of 98) were positive for either keratin 34betaE12 or keratin 7 and 99% (97 of 98) were positive for either keratin 34betaE12, keratin 7 or B72.3. An antibody panel consisting of keratin 7, keratin 34betaE12, chromogranin, and synaptophysin separated 132 of 141 tumors (94%) into distinct groups. We conclude that immunostaining with both neuroendocrine markers and epithelial markers can be useful in the differential diagnosis of lung neoplasms.     

Histidine decarboxylase expression as a new sensitive and specific marker for small cell lung carcinoma.

Histidine decarboxylase is one of the enzymes of the amine precursor uptake and decarboxylation system and is known to be distributed in mast cells and enterochromaffin-like cells. With the hypothesis that histidine decarboxylase expression is a marker for neuroendocrine differentiation, we studied the immunoreactivity of histidine decarboxylase in neuroendocrine cells and tumors of the thyroid gland, adrenal medulla, lung, and gastrointestinal tract. Formalin-fixed paraffin sections were subjected to immunohistochemistry using anti-histidine decarboxylase antibody, and the sensitivity and specificity were compared with those of conventional neuroendocrine markers (CD56, chromogranin A, synaptophysin, and neuron-specific enolase). Enterochromaffin or enterochromaffin-like cells, adrenal chromaffin cells, and thyroid C-cells were positive for histidine decarboxylase, and related tumors (carcinoid tumor, pheochromocytoma, medullary carcinoma) showed a high percentage of positive staining. Furthermore, we used the antibody to distinguish small cell lung carcinoma from non-neuroendocrine lung carcinoma and also to detect neuroendocrine differentiation in large-cell neuroendocrine carcinoma and gastrointestinal small-cell carcinoma. The anti-histidine decarboxylase antibody stained most small cell lung carcinoma (18 of 23, sensitivity 0.78), and was rarely reactive with non-neuroendocrine lung tumors (2 of 44; specificity, 0.95). These values were close to those obtained from CD56 staining (sensitivity/specificity, 0.87/0.98). Histidine decarboxylase was also positive for 6 of 12 large cell neuroendocrine carcinomas and 4 of 7 gastrointestinal small cell carcinomas. In conclusion, we demonstrated that histidine decarboxylase is useful to distinguish between small cell lung carcinoma and non-neuroendocrine carcinoma and to demonstrate neuroendocrine differentiation.     

Genetics of a combined lung small cell carcinoma and large cell neuroendocrine carcinoma with adenocarcinoma

Combined nonneuroendocrine-neuroendocrine lung tumors are relatively infrequent and little is known as for their genetic basis. Here, we report the case of a 69-year-old male with a solitary neoplasm in the upper lobe of the right lung. At histological examination, the tumor showed two components. The main part was an adenocarcinoma of the acinar type. The second part showed morphological and immunohistochemical phenotype of a neuroendocrine carcinoma composed of a small cell lung carcinoma and a large cell neuroendocrine carcinoma. The aim of our study was to investigate the genetic relationship between neuroendocrine and nonneuroendocrine tumor components. To this purpose, we performed a loss of heterozygosity (LOH) analysis with 40 chromosomal microsatellite markers. Microallelotyping revealed a common genetic profile in the different tumor areas. In 9 of 30 informative regions analyzed, LOH involved the same allele in all components, regardless of their histological type and grade. These findings support the true combined nature of this exocrine-neuroendocrine carcinoma of the lung and suggest a common monoclonal origin from a pluripotent epithelial (alveolar or bronchial) precursor cell for the two different tumor components.     

Correlation between histopathological form and the degree of neuroendocrine differentiations in prostate cancer

Prostate cancer (PCa) is the most frequent neoplasic condition in males, but only 64-65% of the cases are sensitive to hormone therapy. The aim of this study was to investigate the neuroendocrine component of the prostatic carcinoma, in relation to the histopathological form and the degree of differentiation. Biopsies were obtained through transurethral resection, from 82 patients with prostate cancer. In order to assess the histopathological form and the Gleason score, one section from each case was stained with Hematoxylin-Eosin. Additional sections were stained with chromogranin A. We considered neuroendocrine cell hyperplasia to have a higher value than that observed in benign prostatic hyperplasia (BPH) and normal prostate (over three neuroendocrine cells÷gland). The quantification of neuroendocrine differentiation (NED) has been significant; the reaction was considered to be weak (2-10% neuroendocrine cells), moderate (10-20%) and intense (over 50%). Cells positive for chromogranin A have been identified in all the cases, but a larger number than that registered in normal tissue has been noted in 59 patients (71.95%). In most of the cases, the neuroendocrine cells have been distributed in small groups among the neoplasic cells, and rarely isolated. In two cases of small cell carcinoma most of the tumoral cells have been positive for chromogranin A. In conclusion, the study of neuroendocrine differentiation in patients with prostatic carcinoma revealed hyperplasia of positive chromogranin A cells, in 71.95% of cases. Neuroendocrine prostatic differentiation is correlated with the advanced stage of evolution and possibly with the resistance to hormonal treatment.     

Immunoexpression of the α subunit of a guanine nucleotide-binding protein (Go) in pulmonary neuroendocrine cells and neoplasms

The α subunit of a GTP-blndlng protein, Go, was investigated in pulmonary neuroendocrine neoplasms and fetal tissues of the lung by an immunohistochemlcal method. Positive immunostaining for the α subunit of Go (Goα) was found predominantly on the cell membrane and found occasionally in the cytoplasm. Typical carcinoids were all positively stained (9/9), and small cell carcinoma showed weaker and less frequent staining (5 positive cases in 10). Atypical carcinoids were variously stained (3/4). The tendency for obvious neuroendocrine differentiation to be immunohistochemically determined in typical carcinoids and not in small cell carcinoma is also true of staining for neuron specific enolase (NSE), chromogranin A (CG-A) and synaptophysin. In the lung, Goα-immunostaining was positive not only in nerve tissues but also in the airway epithelium. In the fetal lung, serial sections immunostained for NSE, CG-A and Goα confirmed that Goα-immunoreactive cells belong to the neuroendocrine cell population. The biological significance of Goα is unclear in normal and neoplastic lung tissues, but Goα is a useful marker of neuroendocrine cells and neoplasms of the lung.     

Immunohistochemical demonstration of chromogranins A and B in neuroendocrine tumors of the lung.

Fifty neuroendocrine tumors of the lung (16 carcinoids, two atypical carcinoids/well-differentiated neuroendocrine carcinomas [WDNCs], 13 neuroendocrine carcinomas of intermediate cell type [SCNCs], and 19 neuroendocrine carcinomas of small cell type [SCNs]) were immunohistochemically investigated with antibodies against chromogranins A and B. All carcinoids and WDNCs were positive for both chromogranins A and B, whereas in cases of ICNC and SCNC both markers were only expressed in six and five cases, respectively. One ICNC was only positive for chromogranin A. In cases of SCNC five tumors were exclusively positive for chromogranin A and six were positive only for chromogranin B. Chromogranins are therefore excellent markers for the immunohistochemical demonstration of carcinoids and WDNCs. It may be speculated that expression of chromogranins in cases of ICNC and SCNC represents a higher degree of differentiation in these tumors.     

Small cell neuroendocrine carcinoma of the urinary bladder

Summary Small cell carcinoma with the histological appearance of pulmonary small cell carcinoma is a rare tumour in the urinary bladder. In previous case reports the neuroendocrine nature of small cell bladder carcinoma has been accepted, but on review the evidence for true neuroendocrine differentiation appears unsatisfactory. In this study the histological, immunohistochemical and ultrastructural characteristics of three cases of small cell carcinoma of the urinary bladder are described. Ultrastructurally, the cytoplasm of all three tumours contained neurosecretory-type granules and each of the tumours demonstrated positive immunoreaction for two or more neuroendocrine markers, from a panel including neuron-specific enolase, chromogranin A, Leu-7, bombesin and synaptophysin. Although the combination of ultrastructural and immunohistochemical examination obviously offers the strongest evidence in establishing neuroendocrine differentiation, it is argued that immunohistochemistry alone may also yield important information in demonstrating a neuroendocrine nature, provided that at least neuron-specific enolase and synaptophysin are included as markers. The clinical relevance of identifying neuroendocrine differentiation in small cell bladder carcinoma is suggested by the favourable response to combination chemotherapy in two of our cases.     

肺神经内分泌肿瘤中INSM1的表达及其临床意义

目的探讨胰岛素瘤相关蛋白1(insulinoma-associated protein 1,INSM1)在肺神经内分泌肿瘤中的表达及其在鉴别诊断中的意义。方法采用免疫组化EnVision两步法检测INSM1、Syn、CgA、CD56在肺小细胞癌(26例)、肺大细胞神经内分泌癌(23例)、肺类癌(23例)、肺腺癌(72例)及肺鳞癌(52例)中的表达。结果(1)INSM1在神经内分泌肿瘤中的总阳性率为87.5%,显著高于肺腺癌(2.8%)和肺鳞癌(1.9%)(P<0.0001)。(2)INSM1在肺小细胞癌和大细胞神经内分泌癌中的敏感性分别为88.5%和78.3%,与Syn(88.5%和82.6%)及CD56(88.5%和78.3%)相似,显著高于CgA(57.7%和39.1%)(P<0.0001);INSM1在肺类癌中的敏感性为95.6%,与传统的神经内分泌免疫组化标志物(Syn、CgA、CD56)相似(P>0.999)。(3)INSM1在肺腺癌和肺鳞癌中的阳性率分别为2.8%和1.9%,与Syn和CgA相比差异无显著性(P>0.05),显著高于CD56(P<0.05)。(4)在37℃1 h孵育一抗,INSM1在小细胞癌、大细胞神经内分泌癌和肺类癌中的阳性率分别为84.6%、52.2%和30%;在4℃孵育一抗过夜,INSM1在三者中的阳性率分别为88.5%、78.3%和95.6%;一抗在4℃孵育过夜条件下,INSM1阳性率均高于37℃1 h的孵育条件。在4℃过夜和37℃1 h两种不同孵育条件下,小细胞癌的检测结果一致性为0.8354,大细胞神经内分泌癌为0.2868,肺类癌为0.0390。结论INSM1是肺神经内分泌肿瘤比较可靠的标志物,在4℃过夜条件下孵育一抗的检测结果比较可信。