Vascular invasion is an adverse prognostic factor in resected non–small‐cell lung cancer

Lung cancer is a leading cause of death, and there is a need for better prognostic factors in treatment decisions. Vascular invasion is a known negative prognosticator, but it is not clear how to evaluate this feature. Here, we studied the prevalence and prognostic impact of blood and lymphatic vascular invasion (BVI, LVI), tumour grade, necrosis, inflammation and pleural invasion on cancer‐specific survival (LCSS) and time to recurrence (TTR) in non–small‐cell lung cancer (NSCLC). A total of 438 patients surgically treated for NSCLC (1993–2010) were examined, including 213 adenocarcinomas (AC), 135 squamous cell carcinomas (SCC) and 90 other NSCLC. BVI and LVI were found in 25% and 21% of the cases, with reduced LCSS and TTR for both markers in AC and SCC (p < 0.005 for all). BVI and LVI remained independent prognostic factors for LCSS and TTR in separate multivariate models for AC and SCC. Combined BVI/LVI (7%) showed significantly reduced LCSS and TTR (p < 0.001), also by multivariate analysis. Our results support that BVI and LVI are valuable for prognostic staging. Vascular invasion identifies a group of patients at higher risk of recurrence and lung cancer–related death, and this could influence stratification of patients for treatment and follow‐up.     

The expression of fatty acid synthase (FASE) is an early event in the development and progression of squamous cell carcinoma of the lung

Correlation of elevated levels of the lipogenic enzyme, fatty acid synthase (FASE), with advanced stages of some cancers has drawn attention to this enzyme as a possible marker of poor prognosis. Because recent studies have shown that cancer cells are dependent on fatty acid synthetic activity and pharmacologic inhibitors of this enzyme are selectively cytotoxic to cancer cells, expression of FASE also may provide a potential target for intervention in the neoplastic process. To determine the potential usefulness of expression of FASE in the neoplastic process of the lung, we evaluated its pattern of expression immunohistochemically in archival specimens from 60 human lung specimens with squamous cell cancer (SCC) and associated "preneoplastic" lesions compared with its expression in the normal bronchial epithelium of 60 noncancer specimens. The expression of FASE was significantly higher in SCC associated uninvolved bronchial epithelium (mean = 0.40+/-0.03, median = 0.38) compared with its expression in the bronchial epithelium of noncancer specimens (mean = 0.18+/-0.02, median = 0.16) indicating its early expression. We also observed a statistically significant step-wise increase in FASE expression from SCC associated uninvolved bronchial epithelium (mean = 0.40+/-0.03, median = 0.38) to epithelial hyperplasia (0.58+/-0.04, median = 0.57) to SCC (1.53+/-0.06, median = 1.50). The results suggested that expression of FASE is an early event in the development and progression of SCC of the lung. The inhibition of fatty acid synthesis by inhibiting enzymatic function with metabolic analogues may be a useful strategy in the treatment of SCCs. The expression of FASE in early lesions such as SCC associated uninvolved bronchial epithelium and epithelial hyperplasia might also provide a potential means for intervention early in the neoplastic process in the lung or even preventing their malignant transformation to invasive carcinomas.     

Expression profiling of integrins in lung cancer cells

Integrins are heterodimeric transmembrane receptors consisting of 18 α and 8 β subunits. Heterodimer composition of α and β subunits has a potential for determining tumor subtypes of human lung cancer. The purpose of this study was to investigate the expression profile of integrins in lung cancer cells. Expression profiling of integrins in a panel of lung cancer cell line, including A549 (adenocarcinoma, ADC), Calu-1 (squamous carcinoma, SCC), H1650 (bronchioloalveolar carcinoma, BAC) and DMS-53 (small cell lung cancer, SCLC), was analyzed by cDNA microarrays, restriction analysis of gene expression (RAGE) and flow cytometry. Seventy-nine lung cancer specimens were used to further validate the data from cell lines using immunohistochemistry. Integrins are obviously expressed in a cell type-specific manner, such as α3 in A549, Calu-1 and H1650 except in DMS53, α4 in H1650, α5 and β1 in all cell lines. The integrins detected with cDNA microarrays were all unequivocally detected with RAGE and by flow cytometry at the protein level. In all lung cancer specimens, α3 integrin was strongly expressed in ADC, SCC and BAC, but was infrequent in SCLC. α4 integrin was solely expressed in BAC. α5 and β1 integrins were expressed in all four histological types of lung cancer specimens. Integrin α3 and α4 may be useful as diagnostic markers for adenocarcinoma, squamous cell carcinoma and bronchioloalveolar carcinoma. RAGE is a promising technique for studying the expression profiles of genes, such as integrins in cancer cells.     

Carcinoma of the lung in Okinawa, Japan: With special reference to squamous cell carcinoma and squamous metaplasia

In Okinawa, a subtroplcal Island In southern Japan, squamous cell Carcinoma (SCC), especially the well-differentiated form, Is prevalent, while this form is relatively rare in both the mainland and other countries (e.g. United States of America). More patlents with SCC from Okinawa, moreover, were positive for human papillomavlrus (HPV) DNA by polymerase chain reaction (PCR) (79%), and harbored HPV types 6, 16 and 18, In combination. On the other hand, less than 30% of the mainland patlents were positive for HPV DNA by PCR. Those patients who were positive all harbored only one HPV type. Furthermore, in Okinawa, there were a signiflcant number of cases with adenosquamous carcinoma, and they too were positive for HPV DNA. The SCC and the adenocarcinoma cells adjacent to the SCC component In these cases were also positive for HPV DNA, and such adenocarcinoma cells were enlarged In size with relatively wide cytoplasm. The authors postulate that HPV infects adenocarcinoma cells and changes them to enlarged cells, followed by squamous metaplasla. In this report, HPV DNA was transfected to adenocarclnoma cells (cultured cell fines) and this showed that HPV causes squamous metaplasla. In addition, aberrant expression of p53 was demonstrated In a large number of the SCC cases In Okinawa. The enlarged adenocarclnoma cells adiacent to the SCC components In adenosquamous carcinomas also showed aberrant expression of p53.The recent advances In the studies of anti-oncogenes, p53, etc. and oncogenes are outlined. It Is to be noted that the molecular mechanisms of carcinogenesis in the lung have been studied In general, classifying lung tumors Into two groups, namely, small cell carcinoma (SCLC) and non-small cell carcinoma (NSCLC). However, because human lung cancer is represented by a wide variety of histological types, molecular genetic studies according to a more detailed histological subclasslflcatlon is needed.     

The expression of Ep-CAM (17-1A) in squamous cell cancers of the lung

Immunotherapy trials using monoclonal antibodies 323/A3 and 17-1A that recognize Ep-CAM, including trials focused on cancer of the lung, currently are underway. Nevertheless, there have been few comprehensive evaluations of the expression of Ep-CAM in specific types of neoplastic processes, including cancer of the lung. The current study of 60 human subjects with squamous cell cancer (SCC) of the lung, selected at random, was undertaken (1) to examine the expression of Ep-CAM in SCC and associated uninvolved bronchial mucosa, bronchial epithelial hyperplasia, and dysplasia, and (2) to correlate the results with established prognostic indicators and survival of patients. In both the uninvolved bronchial mucosa and epithelial hyperplasia, the expression of Ep-CAM in luminal cells was significantly higher compared with its expression in the matched basal cells (P = .003, P < .0001, respectively). When Ep-CAM scores of basal and luminal cells present in uninvolved bronchial mucosa and epithelial hyperplasia were combined, we observed a statistically significant stepwise increase in Ep-CAM expression from uninvolved bronchial mucosa to epithelial hyperplasia to SCC, suggesting its involvement in malignant transformation of SCC. The expression of Ep-CAM was significantly higher in poorly to moderately differentiated SCC compared with well-differentiated SCC (P = .04). An increase in the expression of Ep-CAM with increasing size or local extent of the primary tumor approached statistical significance (P = .09). The expression of Ep-CAM increased significantly with increasing involvement of regional lymph nodes (P = .02). Similarly, the expression of Ep-CAM increased with the increasing TNM stages (P = .04). Kaplan-Meier Survival analysis using the same categorizations showed that increasing tumor size, nodal status, and stage were significantly associated with poor patient survival (P = .04, .01, .01, respectively). There was, however, no statistically significant association between patient survival and staining intensity of carcinomas for Ep-CAM. We conclude that expression of Ep-CAM increased during the progression of SCC of the lung and, therefore, may play a role in the carcinogenesis of this disease.     

Altered global methylation of DNA: an epigenetic difference in susceptibility for lung cancer is associated with its progression

Alterations in global DNA methylation have been observed in many cancers, but whether such alterations represent an epigenetic difference in susceptibility for the disease is unknown. The status of global DNA methylation also has not been reported in intact or specific types of cells involved in the carcinogenic process. To address these issues in lung carcinogenesis, we evaluated the status of global DNA methylation by using a monoclonal antibody specific for 5-methylcytosine (5-mc) in randomly selected lung specimens of 60 cigarette smokers who developed squamous cell carcinoma (SCC) and 30 cigarette smokers who did not. 5-mc immunostaining scores of DNA of SCC (0.61 +/- 0.42) and associated hyperplastic lesions (0.82 +/- 0.27) was significantly lower than those of DNA of histologically normal bronchial epithelial cells (0.99 +/- 0.52) and hyperplastic lesions (1.2 +/- 0.22) of noncancer specimens. The ratio of 5-mc scores between SCC and matched uninvolved bronchial epithelial cells was significantly associated with advanced stage and size of the tumor. The results suggest that alteration in global DNA methylation is an important epigenetic difference in susceptibility for the development of lung cancer. The reduced global DNA methylation in SCC compared with epithelial hyperplasia and its association with tumor size and disease stage is suggestive of its involvement in the progression of SCC. The results also indicate that normal methylation of DNA in epithelial hyperplastic lesions may prevent the transformation of these lesions to invasive cancer. If these results are confirmed, the status of DNA methylation in early lesions such as epithelial hyperplasia could be used to identify smokers who are at risk for the development of SCC.     

Prognostic implication of human papillomavirus infection in squamous cell carcinoma of the lung

On the subtropical island of Okinawa, squamous cell carcinoma (SCC), particularly the well-differentiated form, is the most frequent type of lung cancer, while this form is relatively rare on the Japanese mainland and in other countries. Furthermore, in Okinawa, in 1993, 80% of SCC cases of the lung were found to be infected with human papillomavirus (HPV). We studied the prognosis of SCC of the lung with HPV infection (n = 25) and compared it with non-HPV-infected SCC (n = 16). Using the Kaplan-Meier method (Wilcoxon analysis), the prognosis of HPV-infected cases was found to be better than that of the non-infected cases. In the virus-infected cases, apoptosis and infiltration of a large number of Langerhans cells were demonstrated. In addition to these findings, the virus-infected tumors were demonstrated to be histologically well-differentiated, perhaps contributing to the favorable prognosis. However, among the virus-infected cases, the type 16 virus-infected cases showed a poorer prognosis, compared to those infected with other HPV types. p53 gene mutation was also examined, and was considered to be an unfavorable prognostic factor, as reported elsewhere. However, in Okinawa, HPV-positive cases with p53 mutations showed a slightly better prognosis than did non-viral infected cases with p53 mutations. The TNM staging system was also useful for categorizing the virus-infected cases. The prognosis of stage III (A and B) cases was poor. All of our present cases received surgical treatment. Chemotherapy and radiation therapy were not performed. Such treatment, however, might be effective, because virus-infected uterine cervical carcinomas have been routinely treated with chemotherapy and radiation. Furthermore, if the immunological basis of increased Langerhans cell infiltration in HPV-infected cases is elucidated, a clinical trial with immunotherapy may be favorable for the clinical outcome.     

CD163-positive cancer cells are a predictor of a worse clinical course in lung adenocarcinoma

CD163 is one of the scavenger receptors expressed on macrophages. However, several immunohistochemical studies have demonstrated that CD163 is also detected on cancer cells, and is associated with a poor prognosis. In the present study, we detected CD163 staining on cancer cells in lung adenocarcinoma and squamous cell carcinoma (SCC), and investigated the relationship between CD163 on cancer cells and the clinical prognosis. CD163 staining was seen in 128 of 342 adenocarcinoma cases and 35 of 103 SCC cases. Among the lung adenocarcinoma cases, the progression-free survival and overall survival were significantly shorter in the CD163 high group than the CD163 low group. A similar trend was observed among the SCC cases, but the difference was not statistically significant. Additionally, a higher number of macrophages was detected in areas with CD163-positive cancer cells when compared to areas with CD163-negative cancer cells. In summary, we found that CD163-positive cancer cells are a predictor of a worse clinical course in lung adenocarcinoma and SCC.     

Hyaline globules in ectopic decidua in a pregnant woman with cervical squamous cell carcinoma

Decidual reaction in pelvic lymph nodes has been increasingly documented during pregnancy. This may pose diagnostic difficulty during intraoperative frozen section (FS) and cytological consultation in women undergoing surgical procedures for cervical Squamous cell carcinoma (SCC). A 34‐year‐woman diagnosed to have invasive SCC (stage IB1) of the cervix at 14th week of her first pregnancy underwent abdominal radical trachelectomy and pelvic lymphadenectomy at 22 weeks of gestation. Cytological smears of two of the lymph nodes from intraoperative FS revealed isolated eosinophilic hyaline globules (HG) measuring 45–50 microns, in addition to large polygonal cells with amphophilic cytoplasm and hypochromatic nuclei and occasional squamous‐looking cells with atypical hyperchomatic nuclei. These findings posed a diagnostic dilemma at intraoperative consultation and no definitive diagnosis was rendered. The formlin‐fixed, paraffin‐embedded histological sections of the same lymph nodes showed ectopic decidua with no evidence of metastatic SCC. Decidual cells are a cause of concern for both cytologists and histopathologists. In pregnant women complicated by cervical cancer intraoperative evaluation of pelvic lymph nodes is of utmost importance in order to adopt the optimal conservative treatment modality. In the absence of clear cut evidence of malignancy, a diagnosis of metastatic SCC should not be rendered. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Different histopathology but the same clonality: ALK rearrangement in a patient with metastatic non-small-cell lung cancer

EML4-ALK rearrangement is detected in 2% to 7% of lung adenocarcinomas, these tumors are sensitive to crizotinib. The histologic feature of ALK translocated non-small-cell lung cancer (NSCLC) has been studied, presence of signet-ring cells was a powerful histologic indicator of ALK rearrangement, and this characteristic histology was present both in primary sites and metastases. However, the case we discribed here has different histomorphology in primary sites and metastases, but has the same genotype which both present ALK rearrangement, while absent of EGFR mutation, KRAS mutation and ROS1 rearrangement. This histologic heterogeneity may be a supplement of the histologic feature of ALK rearranged tumor. Moreover, genomic analysis can help distinguish clonal tumors from independent primaries.     

腺鳞癌转化在肺癌耐药中的功能和机制研究

肺癌是一种高致死率的疾病,具有高度的异质性和可塑性。基于病理学分型,肺癌可分为小细胞肺癌和非小细胞肺癌,后者又可细分为腺癌,鳞癌和大细胞癌。临床上可观察到同一个肿瘤内部混合腺癌和鳞癌(腺鳞癌),或小细胞肺癌混合腺癌或鳞癌(混合型小细胞肺癌)。其中,腺鳞癌在临床上占非小细胞肺癌的4%~10%。近几年越来越多的临床案例报道,肺腺癌患者经过化疗、靶向治疗或免疫治疗,肿瘤类型会从腺癌转变成鳞癌,并表现出耐药性。动物模型的研究发现,肝激酶B1(Lkb1)缺失会促进小鼠肺腺癌向鳞癌转化,而腺鳞癌是转化过程的中间态。从细胞起源来看,Club细胞和AT2(Alveolar Epithelial Type 2)来源的肺腺癌可以转化成鳞癌。从分子机制来看,肺腺癌向鳞癌转化的过程中,胞外基质重塑以及代谢重编程会导致细胞氧化应激异常,使得活性氧(Reactive Oxygen Species,ROS)水平急剧上升并诱导p63上调,最终导致腺鳞癌转化并伴随肿瘤耐药。本综述将总结近年来肺腺鳞癌转化领域的进展并阐述其与耐药的关系,以期为深入理解临床肺癌的可塑性奠定理论基础。     

Dihydroartemisinin inhibits cell proliferation via AKT/GSK3β/cyclinD1 pathway and induces apoptosis in A549 lung cancer cells

Lung cancer is the most common cause of cancer-related death in the world. The main types of lung cancer are small cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC); non small cell lung carcinoma (NSCLC) includes squamous cell carcinoma (SCC), adenocarcinoma and large cell carcinoma, Non small cell lung carcinoma accounts for about 80% of the total lung cancer cases. Dihydroartemisinin (DHA) inhibits cell proliferation and induces apoptosis in several cancer cell lines. The effects of DHA on cell growth and proliferation in lung cancer cells remain to be elucidated. Here, we demonstrate that DHA inhibited cell proliferation in the A549 lung cancer cell line through suppression of the AKT/Gsk-3β/cyclin D1 signaling pathway. DHA significantly inhibited cell proliferation of A549 cells in a concentration and time dependent manner as determined by MTS assay. Flow cytometry analysis demonstrated that DHA treatment of A549 cells resulted in cell cycle arrest at the G1 phase, which correlated with apparent downregulation of both mRNA and protein levels of both PCNA and cyclin D1. These results suggest that DHA is a potential natural product for the treatment of lung cancer.     

Metastatic metaplastic breast carcinoma mimicking pulmonary squamous cell carcinoma on fine‐needle aspiration

Metaplastic squamous cell carcinoma (SCC) of the breast is a rare type of breast cancer. Metastases to the lung, which can be a major site of second primary tumor development among breast cancer patients, are difficult to distinguish from primary SCC of the lung and present a unique challenge for pathologists. There are few available discriminating immunohistochemical markers as squamous differentiation typically leads to loss of expression of characteristic primary epithelial cell markers of both breast and lung origin. GATA protein binding 3 (GATA‐3) is a useful marker of breast origin in metastatic ductal and lobular carcinomas including poorly differentiated triple‐negative carcinomas and some metaplastic carcinomas. Here, we present a case of metastatic SCC presenting as a solitary lung mass with regional lymph node metastases and a single satellite lesion in a patient with a history of metaplastic SCC of the breast. In addition to the routine markers of squamous differentiation, the metastases were also positive for estrogen receptor (ER) and GATA‐3 on cytologic material obtained by transbronchial FNA. This suggests that immunoreactivity for ER and GATA‐3 may support a diagnosis of metastatic SCC in the context of a prior metaplastic SCC of the breast. Diagn. Cytopathol. 2015;43:844–849. © 2015 Wiley Periodicals, Inc.     

北京地区汉族人群DNA修复基因XPD单核苷酸多态性与肺癌及食管癌风险的研究

目的：研究核苷酸切除修复基因XPD单核苷酸多态性与北京地区汉族人群肺癌及食管癌风险的关系。方法：采用以医院患者为基础的病例－对照研究方法，包括正常对照383人，肺癌患者351例，食管癌患者325例。以聚合酶链反应－限制性片段长度多态性方法分析了XPD基因Asp312 Asn和Lys751Gln多态性，比较不同基因型与肺癌及食管癌风险的关系，并探讨吸烟与基因多态交互作用对患癌风险的影响。结果：与携带312 Asp/Asp基因型者比较，携带至少1个312Asn等位基因者（即Asp/Asn和Asn/Asn基因型）罹患肺鳞癌的风险增加1．8倍（95％CI1．10－2．93），而与肺腺癌无关（校正的比值比为1．07，95％CI0．55－2．08）。分层分析显示，风险型等位基因312Asn和751Gln与吸烟有明显的交互作用。吸烟剂量≥29包／年且携带312Asn或751Gln者罹患肺鳞癌的风险最高，校正的比值比分别为12．44（95％CI4．97－31．17）和10．74（95％CI4．51－25．57）。XPD基因Asp312Asn和Lys751Gln多态与食管鳞癌风险无关。结论：XPD基因Asp312Asn和Lys751Gln多态是地区汉族人群肺鳞癌遗传易感因素，而与肺腺癌以及食管鳞癌风险无关，可能反映了不同组织学类型肺癌以及肺癌和食管癌之间的病因学差异。     

TPX2在肺鳞状细胞癌及其癌前病变中的表达和意义

目的探讨Xklp2靶蛋白（targeting protein for Xklp2,TPX2）在肺鳞癌及其癌前病变中的表达和意义。方法Westernblot分析TPX2蛋白在2株肺鳞癌细胞系和4株永生化支气管上皮细胞系中的表达。逆转录聚合酶链反应分析21对新鲜肺鳞癌组织及其远端正常肺组织TPX2的mRNA表达水平。构建肺癌组织微阵列,针对其中的319例肺鳞癌患者的组织样品及其相应的114例癌前病变组织的常规石蜡切片进行TPX2免疫组织化学（SP法）染色,结果与临床病理参数比较分析。结果TPX2蛋白在被测肺鳞癌和永生化支气管上皮细胞系中均有水平不一的表达。在新鲜组织标本中76．2％的肿瘤组织较正常组织TPX2 mRNA明显高表达。免疫组织化学分析结果显示,TPX2蛋白的表达在肿瘤组织（64．2％）中明显高于正常组织,且与肿瘤组织病理学分级、临床分期及淋巴结转移相关。TPX2蛋白在肺鳞癌的癌前病变中的表达显著高于正常组织,且随支气管上皮病变程度加重（鳞状化生、不典型增生、原位癌）而增高。结论TPX2蛋白的表达有可能促进支气管上皮癌变和肺鳞癌进展,而且是肺鳞癌淋巴转移的危险因素。TPX2有望成为监测肺鳞癌发生发展的候选标志物。     

Morphology, DNA ploidy and HPV in lung cancer and head and neck cancer

Lung cancer and head and neck cancer have similar genotoxic risk factors. While the vast majority of lung cancers are caused by cigarette smoking alone, smoking together with heavy drinking are the major etiological agents of head and neck cancer. In addition, human papilloma virus (HPV) has been identified as an important causative factor of tonsillar carcinomas. In contrast, chromosomal instability and aneuploidy identifiable by DNA measurement are predominately associated with cancer progression. This selective review summarizes our studies that aimed to gain a better understanding of the biology and pathology of lung cancer and head and neck cancer. In particular, it was attempted (a) to develop a microscopy-based tumor classification system that provides insight into the genetics of cancer cells and in particular their DNA ploidy, (b) to apply this classification system to lung cancer and head and neck cancer and to correlate it with clinicopathological parameters and molecular biomarkers, and (c) to analyze molecular characteristics and in particular the presence of human papilloma virus in lung cancer and head and neck cancer. Therefore, we developed a core classification based on the semi-quantitative assessment of the size and type of tumor cell nuclei and mitoses. It was found that (1) nuclear and mitosis size correlated with the DNA content of the tumor cells, (2) tripolar mitoses were indicative of cancer with near-triploid DNA content, (3) morphological and DNA parameters indicating variability of the cancer genome were associated with poor prognosis of lung cancer patients, (4) HPV-positive head and neck squamous cell carcinomas were characterized by smaller tumor nuclei and reduced DNA amount compared to HPV-negative carcinomas, and (5) HPV is associated with lung cancer in certain geographical regions of the world.     

Small cell carcinoma and carcinoids of the lung: morphology of apoptosis and expression of biomolecular markers of tumor growth

Neuroendocrine lung tumors (NELT) from 50 patients were studied immunohistochemically. Malignant carcinoid and small-cell lung carcinoma (SCC) have a higher level of apoptosis than ordinary carcinoid. An increase of apoptosis index in NELT coincides with an increase in NELT proliferative activity (Ki-67, Bcl-2, c-myc, p-53) as compared to a typical carcinoid. Phagocytosis of apoptotic bodies was absent in SCC. Classic SCC differs from combined SCC by a higher apoptosis index and lower expression of p-53 and Bcl-2. Metastatic SCC differs from SCC without metastases by lower apoptosis level and higher level of proliferative indices (Ki-67, Bcl-2) of tumor cells. Development of unbalance between apoptosis and proliferation may result from mitosis and apoptosis pathology.     

p63基因在肺癌组织中的表达

目的研究肺鳞状细胞癌、腺癌、大细胞肺癌、小细胞肺癌以及淋巴结或肺内转移性肿瘤标本组织中p63基因的mRNA转录因子和蛋白表达水平,探讨p63基因表达与其定位在3q 27-q29区域改变的关系.方法采用cDNA微阵列技术同时检测72例不同病理组织学类型的原发性肺癌(包括鳞状细胞癌、腺癌、大细胞癌、小细胞癌)和肺癌肺内转移及淋巴结转移灶内的p63基因mRNA水平.另外,利用组织芯片技术构建150例原发性肺癌石蜡包埋标本组织芯片,采用免疫组织化学LSAB法检测p63基因蛋白表达情况.同时应用比较基因组杂交(CGH)技术对70例原发性肺癌标本进行了3号染色体长臂改变的分析.结果p63mRNA转录因子在肺鳞状细胞癌标本表达明显增强,与腺癌、大细胞癌、小细胞癌相比增多10倍以上.肺癌转移灶内p63基因mRNA表达水平明显高于其相对应的原发性灶,差异有统计学意义(P＜0.001).免疫组织化学染色结果显示肺鳞状细胞癌阳性表达率为94.64%;腺癌是1.79%;4例大细胞肺癌中2例为阳性染色;但所有小细胞肺癌标本免疫组织化学染色均为阴性.pT1分期肺癌的p63基因蛋白表达阳性率与pT2分期肺癌相比有统计学差异(P＜0.05).比较基因组杂交结果发现肺鳞状细胞癌3号染色体长臂27-29区域有显著的扩增,腺癌表现为缺失.鳞状细胞癌p63基因的表达增强与3q27-q29区域的显著扩增有明显正相关性(P＜0.000 1),说明定位于3号染色体长臂27-29区域的p63基因的拷贝有明显的扩增.结论p63mRNA转录因子和蛋白在肺鳞状细胞癌较其他肿瘤表达显著增高,转移灶高于原发灶;肺鳞癌p63表达增强与3号染色体长臂3q27-q29区域的扩增显著相关.