Advanced stage mucinous adenocarcinoma of the ovary is both rare and highly lethal

BACKGROUND:

Primary mucinous adenocarcinomas of the ovary are uncommon, and their biological behavior is uncertain. Retrospective studies have suggested that many mucinous carcinomas initially diagnosed as primary to the ovary have in fact metastasized from another site. A prospective randomized trial provided an opportunity to estimate the frequency of mucinous tumors, diagnostic reproducibility, and clinical outcomes.

METHODS:

A phase 3 trial enrolled 4000 women with stage III or IV ovarian carcinoma, treated by surgical staging and debulking, with randomization to one of five chemotherapeutic arms. Slides and pathology reports classified as primary mucinous carcinoma were reviewed independently by three pathologists. Cases were reclassified as primary or metastatic to the ovary according to two methods. Overall survival (OS) of reclassified groups was compared within the groups and with that of patients with serous carcinomas.

RESULTS:

Forty‐four cases were classified as mucinous adenocarcinoma upon review. Using either method, only about one third were interpreted by the three reviewers as primary mucinous carcinomas. Reproducibility of interpretations among the reviewers was high, with unanimity of opinion in 30 (68%) cases. The median survival (MS) did not differ significantly between the groups interpreted as primary or metastatic, but the OS was significantly less than that for women with serous carcinoma (14 vs 42 months, P < 0.001).

CONCLUSION:

Advanced stage mucinous carcinoma of the ovary is very rare and is associated with poor OS. Many mucinous adenocarcinomas that are diagnosed as primary ovarian neoplasms appear to be metastatic to the ovary. Cancer 2011. © 2010 American Cancer Society.     

Overexpression of the p53 protein and allele loss at 17p13 in ovarian carcinoma.

Mouse monoclonal antibodies PAb 240 and PAb 1801 which specifically immunoprecipitate p53 protein, were used to examine 27 fresh ovarian tumours (16 serous adenocarcinomas, six endometrioid carcinomas, one mucinous adenocarcinoma, one mucinous borderline tumour and three benign adenomas). Eleven out of 16 (69%) serous adenocarcinomas and one endometrioid tumour showed positive staining with one or both antibodies and none of the mucinous or benign tumours stained with either antibody. DNA from tumour and peripheral blood leukocytes was used to identify allelic deletions on chromosome 17p in tumours. 11/12 positively staining tumours showed less of heterozygosity (LOH) on 17p at the nearest informative locus to the p53 gene. In this series of ovarian tumours, LOH on 17p correlates closely with the aberrant expression of the p53 protein in a high proportion of advanced stage serous adenocarcinomas. This observation suggests that the p53 tumour suppressor gene is involved in the evolution of epithelial ovarian cancer (EOC) and may have prognostic significance.     

Comprehensive allelotype study of ovarian tumors of low malignant potential: potential differences in pathways between tumors with and without genetic predisposition to invasive carcinoma.

Ovarian tumors of low malignant potential (LMP) are intermediate between adenomas and ovarian carcinomas (OC); however, the relevance of LMP to ovarian carcinogenesis is not clear. We performed a comparative analysis of allelotypes in 50 cases of LMP (42 mucinous and 8 serous) and 23 cases of OC (15 mucinous and 8 serous) to investigate any differences in genetic changes. Analysis of loss of heterozygosity (LOH) using 25 microsatellite markers reportedly associated with OC revealed that the total LOH frequency at each marker was significantly lower in LMP than in OC (p < 0.01). However, 9 (36%) loci showed higher LOH frequency in mucinous LMP than in mucinous OC. A genome-wide scan for LOH using 91 microsatellite markers and fine mapping revealed that LOH at D7S1805 (7q35) is characteristic of mucinous LMP (19.4% in mucinous LMP, 8.3% in mucinous OC). We further studied LOH in 3 cases of mucinous OC that were accompanied by mucinous LMP lesions. In 2 cases, LOH frequency was higher in the carcinoma portion than in the morphologically LMP portion. The other case showed microsatellite instability in the morphologically LMP portion and LOH in the carcinoma portion. Our results suggest the presence of an LMP-to-OC developmental sequence and the existence of a subset of LMP that does not develop into OC in the mucinous subtype of ovarian tumors.     

Clinicopathologic characteristics of adenosquamous carcinoma of the lung

Fifty-six cases of surgically resected adenosquamous carcinoma of the lung were studied clinicopathologically, and their outcome was compared with that of adenocarcinomas and squamous cell carcinomas of the lung. The frequency rate of adenosquamous carcinoma was 2.6% of 2160 primary lung cancers resected in the National Cancer Center Hospital (Tokyo, Japan). The survival curves of patients with adenosquamous carcinomas, adenocarcinomas, and squamous cell carcinomas indicated that the outcome of adenosquamous carcinoma was poorer than that of adenocarcinomas and squamous cell carcinomas, particularly in Stages I and II. The amount of adenocarcinoma component did not affect the survival rate, although the histologic features of metastatic lymph nodes was somewhat influenced by the histologic type of the primary tumors. The histologic subtype of adenosquamous carcinoma was one of the independent prognostic determinants.     

Genetic Alterations in Thyroid Tumor Progression: Association with p53 Gene Mutations

To identify the genetic events that must be involved in thyroid tumor progression, we initially investigated p53 gene alterations in 10 papillary adenocarcinomas, 4 follicular adenocarcinomas, and 8 undifferentiated carcinomas. Base substitutional mutations in exons 5 to 8 and loss of heterozygosity (LOH) of the p53 gene were not detected in papillary or follicular adenocarcinomas. However, 7 of 8 undifferentiated carcinomas were carrying base substitutional mutations, and LOH was detected in 3 of 5 informative cases. Furthermore, to verify that the p53 gene alterations are truly involved in tumor progression, DNA from individual foci of the four undifferentiated carcinomas coexisting with a differentiated focus and from one follicular adenocarcinoma with an undifferentiated focus was analyzed by direct sequencing and polymerase-chain-reaction-restriction-fragment-length polymorphism (PCR-RFLP). Base substitutional mutations in the p53 gene from exons 5 to 8 were identified exclusively in the undifferentiated foci, but not in the differentiated foci. LOH was observed in 3 of 4 informative undifferentiated foci. In one of these positive cases, LOH was observed in both papillary adenocarcinoma and undifferentiated carcinoma. However, a p53 gene mutation at codon 248 was detected in the undifferentiated carcinoma but not in the papillary adenocarcinoma. The results imply that LOH occurs first in papillary adenocarcinoma followed by a p53 mutation during the transition from papillary adenocarcinoma to undifferentiated carcinoma. Maintenance of LOH during tumor progression excludes the possibility that these different histological foci are derived from different origins and represents molecular evidence that undifferentiated carcinoma is very likely derived from preexisting papillary adenocarcinoma. Furthermore, these results strongly suggest that the mutated p53 gene plays a crucial role in de-differentiation during the progression of thyroid tumors.     

The prognostic relevance of histologic subtype in appendiceal adenocarcinoma

BackgroundThe aim of this population-based study was to determine the prognostic value of the histologic subtypes mucinous (MAC), non-mucinous (AC) and signet ring cell (SRCC) adenocarcinoma among patients with appendiceal cancer.Methods and materialsData from the Netherlands Cancer Registry (NCR) of patients with primary appendiceal adenocarcinomas with MAC, AC and SRCC histologic subtype, diagnosed between 2001 and 2015 were used (n = 675). To categorize patients according to the recent histopathological classification, the NCR was linked with the Dutch Pathology Registry (PALGA). Log-rank tests and Kaplan-Meier analyses were performed to estimate overall survival (OS), and the cox proportional hazards model was run to identify prognostic factors.ResultsAC was the most frequently encountered histologic subtype (50.9%), followed by MAC (35.8%) and SRCC (13.3%). In locoregional disease, histologic subtype was not a prognostic factor for OS with 5-year survival rates for patients with AC, MAC and SRCC of 60.0%, 60.5% and 69.6% respectively (p = 0.68). Metastatic disease was more common in SRCC (53.8%) than in MAC (38.8%) and AC (23.4%) (p < 0.0001). Median OS for patients with metastatic disease was 12.6, 27.7 and 18.2 months in AC, MAC and SRCC respectively (p < 0.005). MAC was associated with higher survival compared to AC (HR 0.48, 95%CI 0.34–0.69). In subanalyses, MAC was only a positive prognostic factor compared to AC in patients with peritoneal metastases (HR 0.42, 95%CI 0.28–0.62).ConclusionHistologic subtype had no prognostic relevance in locoregional or systemic metastatic disease in appendiceal adenocarcinoma. In peritoneal metastases, mucinous histologic subtype was a favorable prognostic factor, compared to non-mucinous and signet ring cell subtype.     

Prognostic significance of alpha-1-antitrypsin in early stage of colorectal carcinomas

We have previously shown that human colorectal carcinoma cell lines, RCM-1 and CoCM-1, synthesize alpha-1-antitrypsin (alpha 1-AT) in culture. We have studied immunohistochemically the incidence of alpha 1-AT on histologic sections from paraffin-embedded tissues of surgically resected colorectal carcinomas and their metastatic foci, polypectomized adenomas, and normal mucosae. alpha 1-AT was detected in 89 (61%) of 145 carcinomas (including 14 carcinomas in adenoma), and 12 (39%) of 31 adenomas. But only 2 (4%) of 55 normal colorectal mucosae were positive for alpha 1-AT. In metastatic tumor cells of colorectal carcinomas in lymph nodes and other organs, alpha 1-AT positivity was 60% and 82%, respectively. The incidence of alpha 1-AT was markedly higher in advanced adenocarcinomas than in early ones and more frequent in adenocarcinomas of right side (including transverse colon) than those of left side and rectum, regardless of their histological malignancy grades. In mucinous carcinomas the frequency was greater (8 of 9 cases) than in conventional adenocarcinomas. Clinical follow-up of the patients with colorectal carcinomas suggested that alpha 1-AT positivity in Dukes' stage A/B tends to correlate with unfavorable prognosis irrespective of the grade of histologic differentiation of carcinoma, but there is no significant relation in Dukes' stage C/D. Our findings suggest that alpha 1-AT in colorectal carcinoma is related to the invasive and metastatic capacity. It may thus serve as a biologic marker for prognosis of colorectal carcinomas at relatively early stages (Dukes' stage A/B).     

Association of PTEN mutation with HPV-negative adenocarcinoma of the uterine cervix

Serous, mucinous, endometrioid, and clear cell adenocarcinomas arise from reproductive organs of mullerian origin. Although the mutation of PTEN, a tumor suppressor, is known to be involved in tumorigenesis of endometrioid adenocarcinomas of the endometrium and ovary, the role of PTEN alteration in endometrioid adenocarcinoma of the cervix remains to be investigated. To elucidate the molecular pathogenesis of cervical adenocarcinoma and adenosquamous carcinoma, and in particular to examine the potential role of PTEN mutation in endometrioid-type cancer of the cervix, we analyzed 32 cervical adeno- or adenosquamous carcinomas (8 endometrioid adenocarcinomas, 14 mucinous adenocarcinomas and 10 adenosquamous carcinomas) for PTEN mutations and HPV infections. PTEN mutation was detected in 2 of 8 (25.0%) endometrioid cases, 2 of 14 (14.3%) mucinous cases, and none of 10 (0%) adenosquamous cases. HPV DNA was detected in 11 out of 18 (61.1%) PTEN wild-type adenocarcinomas and 8 out of 10 (80.0%) adenosquamous carcinomas. Among 11 HPV-negative adenocarcinomas, 40.0% (2/5) endometrioid cases and 33.3% (2/6) mucinous cases were shown to be PTEN mutated, while no cases (0/21) were PTEN-mutant in the remainder (i.e. adenosquamous carcinomas and HPV-positive adenocarcinomas). The current observations suggest that PTEN mutation is frequently detected in HPV-negative adenocarcinomas of the cervix and the most prevalent occurrence of PTEN mutation in endometrioid subtype is keeping with endometrial and ovarian carcinomas.     

Nuclear reactivity for estrogen. A possible diagnostic tool in differentiating colon cancer metastases in the ovary from primary mucinous ovarian tumors

Tissue distribution of carcinoembryonic antigen (CEA) and estrogen was analyzed in eight primary ovarian mucinous carcinomas, three primary mucinous colonic cancers, and four ovarian metastatic lesions from colonic and pancreatic adenocarcinomas. Primary ovarian mucinous carcinomas and metastatic colonic carcinomas had similar localization of CEA within the epithelial cytoplasm. Estrogen localization, in contrast, was shown within the epithelial nuclei of seven of eight primary ovarian mucinous tumors; whereas the nuclei of metastatic and primary mucinous colonic carcinomas did not have intranuclear estrogen. The cytoplasm and the stroma of both primary ovarian and metastatic colonic carcinomas stained for estrogen.     

Primary malignant neoplasms of the appendix: a population-based study from the surveillance,epidemiology and end-results program, 1973-1998

BACKGROUND: Cancer of the appendix is an uncommon disease that is rarely suspected rarely before surgery. Although several case series of these tumors have been published, little research has been anchored in population-based data on cancer of the appendix. METHODS: This analysis included all actively followed cases of appendiceal neoplasms reported to the National Cancer Institute's Surveillance, Epidemiology and End-Results (SEER) program between 1973 and 1998. Tumors were classified as "colonic type" adenocarcinoma, mucinous adenocarcinoma, signet ring cell carcinoma, goblet cell carcinoid, and "malignant carcinoid" (SEER only collects data on carcinoids specifically classified as malignant). We compared incidence, overall survival and survival rates by extent of disease at diagnosis. RESULTS: Between 1973 and 1998, 2117 appendiceal malignancies were reported to the SEER program, of which 1645 cases were included in the analysis. Age-adjusted incidence of cancer of the appendix was 0.12 cases per 1,000,000 people per year. Demographic characteristics of patients with goblet cell carcinoid tumors were midway between those of patients with malignant carcinoid and all types of adenocarcinomas. After controlling for age and extent of disease at diagnosis, the overall survival rate for patients diagnosed between 1983 and 1997 (n = 1061) was significantly worse for those with signet ring cell carcinoma than for those with any other tumor type (P < 0.01). In addition, overall survival rates were better for patients with malignant carcinoid (P = 0.01).CONCLUSIONS: Demographic characteristics of patients with cancer of the appendix vary by histology. Except for signet ring cell carcinoma and malignant carcinoid, the extent of disease at time of diagnosis is a more important predictor of survival than histology.     

K-ras activation in neoplasms of the human female reproductive tract

The role of cellular oncogenes in the development of epithelial tumors of the human female reproductive tract has not previously been extensively studied. DNAs isolated from ten human uterine, 13 ovarian, and four cervical neoplasms and from three cell lines derived from endometrial adenocarcinoma were investigated by dot blot hybridization after polymerase chain reaction amplification of ras gene sequences and in some cases by NIH 3T3 transfection. Transforming activity was found in two of nine endometrial adenocarcinomas, but none of seven ovarian carcinomas and none of four cervical carcinomas showed transforming activity. K-ras sequences with a GGT----GAT mutation in codon 12 were demonstrated in both transformants derived from endometrial carcinoma. K-ras codon 12 mutations were similarly detected in six of 13 endometrial carcinomas (one GAT and GCT, one GTT and GCT, two GAT, two GTT) and two of 13 ovarian tumors (GAT and GCT, GAT), both mucinous adenocarcinomas. Point mutation of K-ras in codon 12 is thus comparably frequent in uterine endometrial carcinomas and in colorectal carcinomas and may have similar significance as an event that contributes to progression of these tumors. Cervical carcinomas and ovarian tumors in general, with the possible exception of mucinous adenocarcinoma of the ovary, do not appear to have this characteristic.     

Adnexal carcinomas of the skin. I. Eccrine carcinomas

The diagnostic identification of sweat gland carcinomas is hampered by their rarity and their histologic resemblance to various visceral tumors, leading to confusion with metastatic lesions. In this series, 14 cases of eccrine carcinoma in five male and nine female patients, ranging in age from 13 to 84 years, are described. Ten tumors strongly resembled infiltrating ductal adenocarcinomas of the breast, and were thus classified as ductal. Three had a prominent mucinous matrix, similarly explaining their categorization as mucinous carcinomas. Finally, one neoplasm was a classic eccrine porocarcinoma. Four patients with ductal eccrine carcinomas suffered metastasis, and a 50% mortality rate was observed among this group of ten cases. In contrast, only one of three mucinous carcinomas metastasized, although all of these lesions recurred locally, as did the single porocarcinoma. None of the latter four neoplasms proved fatal. The results of conventional special stains in these 14 cases are discussed, and histologic features that they shared, and which may be utilized in distinguishing eccrine carcinomas from benign sweat gland tumors, are presented.     

Prevalence of BRCA1 and BRCA2 mutations in unselected breast cancer patients from Greece

Carcinomas of the appendix are exceedingly rare tumors and have an annual age-adjusted incidence of around 0.4 cases per 100,000. Appendiceal adenocarcinoma accounts for < 0.5% of all gastrointestinal neoplasms and, of these, mucinous adenocarcinomas account for the majority. Published accounts of familial instances of primary appendiceal tumors are strikingly rare. We report two siblings who both developed primary mucinous adenocarcinomas. A genetics evaluation was conducted to determine if there was a recognizable underlying single gene disorder; no DNA mismatch repair defect was evident, and no other diagnosis was apparent. A review of appendiceal cancers seen at Mayo Clinic from l997 to the present was conducted to search for additional familial cases. Among 316 cases of primary appendiceal cancer of any histologic type, this sib pair was the only family reporting a second affected family member. The occurrence of appendiceal cancer in siblings may represent a random occurrence. An exceedingly rare predisposition syndrome cannot be ruled out.     

Genetic heterogeneity of surgically resected prostate carcinomas and their biopsy specimens is related to their histologic differentiation

BACKGROUND: In human prostate carcinogenesis, many genetic analyses including conventional loss of heterozygosity (LOH) studies and microsatellite LOH analyses using the polymerase chain reaction method have revealed frequent LOH events at specific regions on chromosomes 3p, 7q, 8p, 10q, 16q, 17q, and 18q. METHODS: Using the laser-captured microdissection method, the authors extracted genomic DNA from 23 cases of prostate carcinomas including 59 different lesions and 8 biopsy specimens. Using (32)P-labeled primers, the authors analyzed six microsatellite loci (D3S647, D3S1228, D7S522, D8S137, NEFL, and D10S190) at which frequent LOH events have been reported. RESULTS: Of 10 cases in which the authors found LOH at any of the loci, 8 cases showed a heterogeneous LOH pattern. In four cases, the authors also found replication error (RER) at some of the loci examined. There was no significant relation between histologic differentiation and frequency of LOH or RER events. The overall LOH rate was found to be significantly lower in foci at classification pT2 (1 of 28 foci, 3%) compared with those at classification pT3 (13 of 44 foci, 30%). In pT3 samples, LOH events in extraglandular foci (9 of 23 foci, 39%) tended to be more frequent compared with those in intraglandular foci (8 of 41 foci, 20%). The patterns of LOH events in biopsy specimens correlated well with those in foci from surgical material showing the same histologic characteristics. CONCLUSIONS: Prostate carcinoma is a genetically multicentric carcinoma, and the genetic heterogeneity is well correlated with histologic differentiation. The frequency of LOH events increased according to the degree of tumor progression.     

Frequent loss of heterozygosity at 1p36 in ovarian adenocarcinomas but the gene encoding p73 is unlikely to be the target.

Loss of heterozygosity (LOH) involving the distal part of the short arm of chromosome 1 occurs frequently in ovarian adenocarcinomas but the tumour suppressor gene(s) targeted by this event is unknown. We have used five microsatellite markers in a panel of 56 ovarian adenocarcinomas to determine which part of 1p34 - 36 is the focus of this LOH. LOH was considerably more common at 1p36 (43%) than at 1p34 - 35 (18%), and 11 tumours showed LOH at 1p36 but not at 1p34 - 35. These data strongly suggest the presence of a tumour suppressor gene inactivated in ovarian adenocarcinoma at 1p36. The p53 homologue, p73, has recently been isolated and mapped to 1p36 and therefore is a candidate for this tumour suppressor gene. However, RT - PCR and Western analyses revealed strong expression of p73 in ovarian adenocarcinoma cell lines but very low or undetectable levels in normal ovarian surface epithelial cells. Immunohistochemical analysis of primary ovarian tumours showed that only 3/22 (14%) contained p73 expressing cells. There was no association between 1p36 LOH and p73 expression in ovarian tumours, nor between p73 and p53 expression. These findings strongly suggest that p73 is not the target of 1p36 LOH in ovarian adenocarcinomas but indicate the presence of an, as yet unidentified, tumour suppressor gene in this region that plays an important role in ovarian tumorigenesis.     

卵巢癌及宫颈癌中17p13.3的杂合性丢失

目的探讨染色体１７ｐ１３．３的杂合性丢失（ＬＯＨ）与卵巢癌、宫颈癌发生及发展之间的相关性。方法采用ＰＹＮＺ．２２探针做Ｓｏｕｔｈｅｒｎ印迹技术,检测２４例卵巢癌、９例宫颈癌及１３例妇科非癌患者手术切除组织染色体１７ｐ１３．３的ＬＯＨ。结果１２例卵巢癌（包括１例交界性粘液性囊腺癌）和４例宫颈癌发生１７ｐ１３．３的ＬＯＨ,丢失频率分别为５０．０％和４４．４％。１３例非癌组织中,仅１例（７．７％）发生丢失,该例经病理证实为宫颈上皮内瘤变Ⅲ级,属癌前期病变（Ｐ＜０．０１）。结论染色体１７ｐ１３．３的ＬＯＨ可能与宫颈癌和卵巢癌的发生相关,检测１７ｐ１３．３的杂合性丢失将有助于深入了解卵巢癌和宫颈癌发生及发展的分子基础。     

Allelotype of non-small cell lung carcinoma--comparison between loss of heterozygosity in squamous cell carcinoma and adenocarcinoma.

We examined loss of heterozygosity (LOH) on all autosomal chromosomes in 53 non-small cell lung carcinomas. Frequent LOH was observed on the long arms of chromosomes 1 (37%), 2 (31%), 5 (30%), 8 (31%), and 13 (32%), and the short arms of chromosomes 3 (54%) and 17 (62%). LOH on chromosomes 3p and 17p was observed in all informative cases of squamous cell carcinoma, but was significantly less frequent in adenocarcinomas (P = 0.003 and 0.001, respectively). Similarly, LOH on chromosome 13q was observed frequently in squamous cell carcinomas (5 of 9 informative cases, or 56%), but in only 5 of 26, or 19%, of adenocarcinomas. In contrast, LOH on chromosome 2q was observed only in adenocarcinomas. In addition, this chromosomal arm was lost more frequently in poorly differentiated, compared to well differentiated adenocarcinomas. Furthermore, a correlation between fractional allelic loss and pathohistological grade was identified. These results implicate the presence of several tumor suppressor genes associated with development and/or progression of non-small cell lung carcinomas.     

Clinical characteristics and prognostic factors for primary appendiceal carcinoma

Aim: Primary adenocarcinoma of the appendix is a rare malignancy. This study assessed prognostic factors affecting the clinical outcome in patients with appendiceal neoplasms. Methods: We performed a retrospective analysis of patients who had appendectomies between 1991 and 2007 at five centers in South Korea. Results: Overall 55 patients (19 men, 36 women, median age 61 years) were identified. Of these, 37 (67.3%) were mucinous adenocarcinomas, 14 (25.5%) were intestinal‐type adenocarcinomas, and four (7.3%) were signet ring cell carcinomas. The distribution of stages was: 26 (47.3%) with localized disease, five (9.1%) with regional disease, and 24 (43.6%) with distant metastatic disease. The overall 3‐ and 5‐year survival rates among all patients were 72.2% and 64.0%, respectively, with 20 deaths during the follow‐up period. In a multivariate analysis, high histological grade (hazard ratio [HR]vs low grade 15.7; P = 0.001) and pathological stage (distant vs loco‐regional, HR 6.2; P = 0.021) were independent predictors of overall survival. Of the 34 patients who underwent curative resections of primary appendiceal carcinomas, the 3‐ and 5‐year disease‐free survival rates were 66.4% and 53.3%, respectively. The recurrence rate was higher in patients with regional lymph node metastasis (HR vs node negative disease 23.4; P = 0.005) and high‐grade tumors (HR vs low grade 6.3; P = 0.029). Additionally, a right hemicolectomy reduced the risk of recurrence (HR vs lesser procedures 0.05; P = 0.005). Conclusion: High tumor grade and advanced stage were significantly predictive of poor survival outcome in patients with primary appendiceal carcinomas.     

LOSS OF HETEROZYGOSITY ON CHROMOSOME 17p13.3 IN OVARIAN CANCER AND CERVICAL CANCER

ＣａｒｃｉｎｏｇｅｎｅｓｉｓｃｏｎｓｉｓｔｓｏｆｍｕｌｔｉｐｌｅｑｕａｌｉｔａｔｉｖｅｌｙｄｉｆｆｅｒｅｎｔｓｔｅｐｓｉｎｗｈｉｃｈａｃｃｕｍｍｕｌａｔｉｏｎｏｆＤＮＡａｌｔｅｒａｔｉｏｎｏｃｕｒｓａｎｄｃｒｉｔｉｃａｌｅｖｅｎｔｓ，ｉｎｖｏｌｖｉ...     

肺癌中ING1基因变化及其表达水平的研究

目的：检测肺癌中抑癌基因ING1微卫星杂合性缺失（LOH）及其主要蛋白产物p33^ING1b的表达情况，以探讨ING1基因改变-9肺癌发生发展的关系。方法：采用银染PCR—SSCP法检测肺癌组织ING1基因微卫星LOH发生的频率；应用组织芯片技术和免疫组化方法，检测肺癌p33^ING1b蛋白表达水平。结果：70例肺癌组织ING1基因4个微卫星位点的总杂合性缺失率为55．7％（39／70），并且越靠近ING1基因位点，发生率越高，但与临床病理参数无关。217例肺癌p33^ING1b蛋白的LOH发生率为47．0％（102／217），鳞状细胞癌高于腺癌、腺鳞癌和细支气管肺泡癌（P〈0．05），其余类型间差异无显著性（P〉0．05）；p33^ING1b的表达与其他临床病理参数不相关（P〉0．05），但与LOH发生频率相关（P〈0．05）。结论：p33^ING1b蛋白在肺癌组织中存在高频率的低表达或失表达，并且ING1基因的微卫星LOH发生频率也很高。推测LOH是该基因异常表达的重要原因，其结果可能导致该基因的下调和（或）蛋白质功能的失活，从而丧失其对细胞的生长抑制作用，促进了肿瘤的发生。