肝细胞癌临床病理学特征与p53蛋白表达的关系

应用免疫组织化学技术检测29例肝细胞癌（肝癌）和23例肝硬化标本中突变型p53蛋白的表达，并探讨后者与肝癌临床病理学特征之间的关系。结果：肝癌突变型p53蛋白表达阳性率为70％（20／29），癌旁组织阳性率为60％（18／29），肝硬化组织阳性率为30％（7／23），有血管侵犯的12例肝癌变变型p53蛋白表达均为阳性，而无血管侵犯的17例中仅8例为阳性（P＜0．05）；突变型p53蛋白阳性组血清甲胎蛋白（AFP）明显高于阴性组（8370±4764ng／ml比98．7±64．3ng／ml，P＜0．05）。提示：P53蛋白表达在肝硬化时即发生了异常；p53蛋白异常可能是AFP基因被激活的原因之一；p53蛋白异常有利于肝癌向门静脉转移。     

BRCA1和相关凋亡调控蛋白在人乳腺浸润性导管癌中的表达与相关性分析

目的：分析乳腺癌易感基因（BRCA1）和相关凋亡调控蛋白C-myc、Bcl-2和p53在乳腺浸润性导管癌中表达的相关性，与临床病理指标的关系，探讨BRCA1等蛋白表达对乳腺癌诊断和治疗的意义。方法：免疫组织化学SP法，检测24例乳腺良性病变和120例乳腺浸润性导管癌中BRCA1、C-myc、Bcl-2和p53的表达，收集患者临床资料，校正Pearsonx。检验进行统计分析。结果：在良性乳腺病变，BRCA1、C-myc和p53蛋白在细胞核的阳性表达率分别为95．8％（23／24）、8．3％（2／24）和4，2％（1／24），Bcl-2在细胞质／膜阳性表达率为91．7％（22／24）；在浸润性导管癌，BRCA1、C-myc和p53蛋白阳性表达率分别为60．0％（72／120）、38．3％（46／120）和36．7（44／120），Bcl-2阳性表达率为50．8％（61／120）；与良性乳腺病变比较，浸润性导管癌中BRCA1、Bcl-2阳性表达率明显降低，C—myc和p53表达增加，均有显著性差异（P〈0．05）。BRCA1表达与C—myc和p53过表达相关；C—myc表达与p53表达相关；BRCA1、p53、C—myc表达与Bcl-2表达均无显著相关性。BRCA1、C-myc和Bcl-2表达与组织分级和腋淋巴结转移相关。结论：乳腺浸润性导管癌中，BRCA1失表达与C—myc和p53过表达、组织学分级和腋淋巴结转移相关，凋亡调控基因的异常表达参与乳腺浸润性导管癌的发生。     

肺肿瘤演进中cyclinD1、p53基因表达的实验研究

目的：探讨乙酰胆蒽（20-MC)诱导小鼠肺肿瘤发生、发展过程中cyclinD1和p53基因表达特点及其意义。方法：小鼠腹腔内注射20－MC，在不同时间段处死小鼠，得到肺部病变共292个，其中上皮增生（HP）31个，肺泡细胞腺瘤（AA）145个，乳头状腺瘤（PA）61个，乳头状腺癌（PC）55个及其复合性病变。应用免疫组化法检测各型病变中cyclinD1、p53基因蛋白表达情况。结果：cyclinD1癌基因蛋白在HP、AA、PA及PC中均有表达，分别为86％（6／7）、87％（89／102）、73％(41／56）及68％（17／25），cyclinD1癌基因蛋白在良性病变的表达强于恶性病变（x^2=5．531，P＝0．033）。p53抑癌基因蛋白表达于腺癌组织、有明显异型性的细胞、肿瘤进展较晚期，PC、PA和AA阳性率分别为40％（16／40）、9％（6／69）和3％（4／121），且分布方式不同，HP无表达。癌组织中p53基因表达明显强于各良性病变（x^2＝41．77，P＝0．000），各型病变中以PC的cyclinD1、p53基因均阳性的比率较高,为26％，HP和AA中两基因无共同表达。结论：cyclinD1基因可能参与调控肺肿瘤发生过程，而p53抑癌基因突变则与细胞增恶、肿瘤进展等有密切关系。     

102. 人1 673例恶性肿瘤764例良性病变中P53基因异常改变的免疫组化研究

目的：抑癌基因P53的突变、被降解或丢失在人类多种恶性肿瘤病的发生发展中具有重要作用。研究这种变化的规律及其调控环节，可为肿瘤病的有效防治提供可靠的分子病理学依据。方法：对人1 673例不同恶性肿瘤及764例不同良性病变分别进行单克隆抗P53蛋白免疫组化检测（LSAB法）。结果：恶性肿瘤组织P53蛋白阳性率56.1%(939／1 673)，良性病变7.85%（60／764），两者有极显著差异（P＜0．001）；在恶性肿瘤中，鳞癌阳性率62．9％（387／615）、腺癌55.9%(320/572)其他恶性瘤(包括颅内原发肿瘤，黑色素瘤，骨肉瘤、生殖细胞瘤等)47.7％(232／486）均分别高于相应组织的良性病变，相差极显著(P＜0．001）；恶性肿瘤中，以睾丸恶性生殖细胞瘤的阳性率81．0％(47／58）最高，而恶性程度很高的颅内髓母细胞瘤最低，仅3．9％（2／51）；良性病变以喉鳞状上皮乳头状瘤、结肠腺瘤或及不典型增生病变阳性率较高，可达16％。但良性瘤变中P53蛋白阳性细胞的染色强度与细胞密度明显低于恶性肿瘤。值得注意的是正常睾丸的曲细精管内的不同发育阶段的生精细胞，其阳性率高达40％（6／15）。虽然阳性细胞数稀少也应重视。结论：①P53基因突变或其他异常改变在人细胞恶性转化与肿瘤形成中具有重要作用；②不同类型肿瘤P53蛋白变化的差异，反映了多种不同癌基因或及抑癌基因在肿瘤发生过程的不同作用。髓母细胞瘤等恶性肿瘤的发生、发展可能是P53基因以外的基因异常调控的结果；③应用免疫组化染色可检测细胞原位的基因或其调控分子异常改变；对肿瘤的理论研究、临床应用都是很有用处。     

胃癌组织中p53基因突变及p53和mdm2蛋白表达的研究

目的：探讨mdm2和p53基因异常在胃癌发生发展中的作用以及两者相关性。方法：应用免疫组化技术检测58例胃癌组织以及相应癌旁组织中mdm2和p53蛋白的表达；PCR-SSCP银染技术检测p53基因exon5～8突变情况。结果：胃癌组p53和mdm2蛋白阳性率分别为86．21％（50／58）和29．31％（17／58），癌旁组织组p53和mdm2蛋白均为阴性，胃癌组p53和mdm2蛋白阳性率明显高于癌旁组织组，两两间差异有统计学意义，P=0．0000、P=0．0001。胃癌组织中p53和mdm2蛋白表达率与肿瘤大小、组织学类型、分化程度、淋巴结转移以及患者年龄等无显著相关性，P〉0．05。mdm2蛋白阳性表达与p53蛋白过表达呈显著正相关,X^2=11．1839，P=0．0008，r=0．4391。2例胃癌组织检测到p53基因突变，突变均位于exon5，58例相应癌旁组织均禾检测到p53基因突变。结论：mdm2和p53蛋白异常表达与胃癌发生有关，p53基因突变可能并非胃癌组织中p53蛋白异常累积的主要原因，mdm2蛋白在胃癌发生发展中的作用可能与p53蛋白密切相关。     

增殖细胞核抗原和p53蛋白在胆囊癌中的表达

本文应用PCNA和p53抑癌基因蛋白的免疫络化方法，对11例胆囊上皮良性病变和33例胆囊癌进行了研究，结果发现胆囊良性病变和胆囊癌的平均PCNA指数分别为：良性病变为24．1％（n＝11．x±24．6），高分化癌为48．0％（n＝13，x±12．8），中分化癌为49．5％（n＝11，x±15．4）．低分化癌为76．4％（n＝9，x±18．1）；高分化胆囊癌平均PCNA指数明显高于良性病变（P＜0．05）；低分化癌的平均PCNA指数明显高于高分化癌（P＜0．05）；11例胆囊上皮良性病变均无p53蛋白阳性表达；33例胆囊癌p53阳性表达12例（36．4％），高分化癌p53阳性率为15．4％（2／13）．中分化癌45．5％（5／11）．低分化癌55．6％（5／9）：各组阳性率比较无显著性差异（P＞0．05）；PCNA指数≥50％的胆囊癌其p53蛋白阳性率明显高于PCNA指数＜50％的胆囊癌（P＜0．05）。结果提示：PCNA指数与胆囊癌的分化程度有关．PCNA及p53蛋白的免疫组化染色对胆囊上皮良、恶性病变的鉴别论断有帮助。本文还就胆囊癌p53蛋白表达与PCNA指数的关系进行了讨论。     

端粒酶活性表达及p53异常在非小细胞肺癌中表达及临床意义

目的：研究端粒酶活性及 p53异常在非小细胞肺癌 (nonsmall cell lung cancer, NSCLC)中的表达及其相互关系。方法：用端粒重复扩增（ telomeric repeat amplification protocol, TRAP）法检测 NSCLC组织、癌旁非癌肺组织、肺良性病变组织端粒酶活性,用 Western blot印迹法检测 NSCLC组织 p53蛋白表达。结果：端粒酶活性表达率为： NSCLC 93.02％ (80/86),癌旁非癌肺组织 9.33％ (7/75),肺良性病变组织 27.27％ (3/11), NSCLC组织端粒酶活性表达率显著高于癌旁非癌肺组织及肺良性病变,端粒酶活性表达率在不同组织类型、细胞分化、肿瘤大小、病理分期间差别不显著; NSCLC p53异常为 51.42％（ 36／ 70）, p53异常在Ⅰ、Ⅱ期与Ⅲ、Ⅳ期之间,Ⅰ级与Ⅱ、Ⅲ级之间差异有统计学意义;端粒酶活性表达与 p53异常无显著关联（ P >0.05）;结论： NSCLC标记物中,端粒酶活性表达较 p53敏感, p53对 NSCLC分期分级有帮助,端粒酶活性表达与 p53异常在 NSCLC发生发展中可能是两个独立的因素。     

食管鳞癌中p16基因启动子区甲基化及其表达

 目的探讨食管鳞癌（ESCC）p16基因甲基化的状况及其表达与食管鳞癌临床病理特征之间的关系。方法采用甲基化特异性PCR方法（MSP）分别检测75例食管癌组织、癌旁组织和切缘组织p16基因启动子区域CpG岛甲基化状态。采用Envision免疫组化法检测食管癌组织及癌旁组织的p16蛋白的表达。结果75例标本中，食管癌组织、癌旁组织和切缘细织p16基因甲基化率分别为41．3％（31／75）、13．3％（10／75）和6．67％（5／75）。癌组织和癌旁组织P16蛋白的阳性表达率分别为29．3％（22／75）和56．7％0（17／30）。31例癌组织p16基因甲基化阳性标本中有2例（6．4％）检测到P16蛋白的表达，而44例癌组织p16基因甲基化阴性标本中有20例（45．5％）检测到P16蛋白的表达。食管癌组织p16基因甲基化率显著高于癌旁组织和切缘组织（P〈0.01），P16蛋白表达与p16基因甲基化呈负相关。p16基因启动子区甲基化与食管癌的组织学分级、肿瘤部位无明显相关，与临床分期、淋巴转移密切相关。结论p16基因甲基化在食管癌发生发展中起着重要作用，食管鳞癌的分期和淋巴结转移与p16基因甲基化之间有密切关系。     

广西地区肝细胞癌患者组织中p53蛋白表达的研究

目的：探索广西肝癌高发区肝细胞癌（HCC）的组织中检测p53蛋白的表达情况。方法：用免疫组织化学方法对30例肝细胞癌（HCC）和癌旁组织进行检测。p53蛋白的免疫组化染色一抗用的是兔抗。连续切片染色乙型肝炎表面抗原和核心抗原。结果：30例肝细胞癌组织中有13例（13／30,43.3％）p53蛋白表达阳性;在≤5.0的肝细胞癌组织中有25％（1／4）的p53蛋白表达阳性;在＞10.0cm的肝细胞癌组织中有71.4%(5/7)的p53蛋白表达阳性。p53蛋白阳性在中、低分化肝细胞癌中的表达高于在高分化肝细胞癌组织中,而且大多数在年轻患者的肝细胞组织中。结论：本组资料表明,p53蛋白表达与肿瘤的大小、分级和患者的年龄有着密切的关系。30例中有27例（90.0％）证实为HBV感染,表明p53蛋白表达与性别和HBV感染、肝硬化及AFP水平无密切相关关系。     

p16和Rb基因在人肝细胞癌中的表达

目的：分析p16基因和视网膜母细胞瘤基因（Rb）在人肝癌细胞中表达的改变。方法：用免疫组织化学方法40例肝细胞癌和癌旁组织进行检测。结果：肝组织中的p16蛋白和Rb蛋白的异常表达分别为94．44％（34／36）和45．71％（16／35）。p16蛋白阴性或弱阳性而Rb呈强阳性者13例（13／34,38．23％）,两者的表达呈负相关关系。p16和Rb蛋白均异常者15例（15／34,44．11％）,表明Rb蛋白表达的调节除p16外,还有其他途径。二者的异常表达与肝癌的恶性程度无相关关系。结论：细胞调节因子p16和Rb基因的异常表达,均参与肝细胞癌的发生。以p16蛋白表达的改变为主。     

Dietary N-acetyl-L-cysteine modulates benzo[a]pyrene-induced skin tumors in cancer-prone p53 haploinsufficient Tg.AC (v-Ha-ras) mice

Epidemiologic studies support the protective role of dietary antioxidants in preventing cancer. However, emerging evidence from clinical trials and laboratory data suggest that in some cases individual antioxidant supplements may actually exacerbate carcinogenesis. Our goal was to explore these paradoxical activities in a rodent model that possesses genotypic characteristics of human cancers. We selected the p53 haploinsufficient Tg.AC (v-Ha-ras) mouse as a model, because it contains an activated, carcinogeninducible ras oncogene and an inactivated p53 tumor suppressor gene, which are frequent genetic alterations in human cancers. These mice develop chemically induced benign and malignant skin tumors rapidly which can easily be quantified. Mice were fed basal diets with or without 3% N-acetyl-L-cysteine (NAC), a well-recognized antioxidant, prior to, during and after topical application of the carcinogen benzo[a]pyrene (64 microg/mouse) applied twice per week for 7 weeks. Tumor incidence exceeded 90% for both groups, and NAC did not reduce tumor latency. Mice fed NAC displayed a 43% reduction (P < 0.05) in tumor multiplicity and delayed the appearance of lesions (P < 0.05). Dietary NAC also significantly (P < 0.05) improved group survival by 5 weeks. Total tumor yields were reduced in both dietary groups but malignant spindle cell tumors (SCT) increased by 25% in NAC-fed mice. The v-Ha-ras oncogene and p53 protein products were clearly co-expressed in both benign and malignant lesions from both dietary groups. In summary, dietary supplementation with NAC was chemopreventive, but the marginal increase in SCT suggests a paradoxical effect.     

食管鳞状细胞癌p16和nm23-H1基因蛋白表达及意义

目的 :探讨多肿瘤抑制基因p16蛋白和nm2 3 H1基因蛋白在人食管癌的表达及与肿瘤生物学行为的关系。方法 :应用免疫组织化学方法观察 51例食管鳞状细胞癌及其淋巴结转移癌中p16蛋白的表达 ,结合观察转移抑制基因nm 2 3 H1的表达。结果 :p16在食管鳞状细胞癌中呈低表达 ( 4 5 1% ,2 3/51) ,阳性率显著低于正常食管粘膜及癌旁组织 (P <0 0 1) ,阳性率与分化程度相关 (P <0 0 1) ,Ⅰ级66 7% ( 14/ 2 1) ,Ⅱ级 34 8% ( 8/ 2 5) ,Ⅲ级 14 3% ( 1/ 7) ;与肿瘤浸润、转移无关。nm 2 3 H1的阳性率为60 8% ( 31/ 51) ,与浸润深度呈负相关 (P <0 0 5) ,淋巴结转移癌的阳性率 ( 18 8% ,3/ 16)显著低于食管癌原发灶 (P <0 0 1)。p16与nm 2 3 H1的表达无关。结论 :p16蛋白在食管癌的低表达提示有频发性的p16基因失活 ,且与肿瘤分化有关。nm2 3 H1与食管癌的浸润 ,转移相关。p16和nm 2 3 H1的失活在食管癌的形成及发展中可能起不同的作用     

Association of p53, K-ras and proliferating cell nuclear antigen with rat lung lesions following exposure to simulated nuclear fuel particles.

Expression of p53, K-ras, and proliferating cell nuclear antigen (PCNA) and mutations of p53 and K-ras genes in lung lesions of Han/Wistar rats were investigated by immunohistochemistry and direct DNA sequencing following a long-term exposure of animals to neutron-activated UO2 particles. The p53 protein was overexpressed in all five malignant tumors, in 62% of benign tumors, and in 42% of hyperplastic lesions examined. K-ras protein and PCNA levels were only slightly elevated in all types of lung lesions. In three malignant tumors a C-->T transition was detected in codon 288 (human 290) of the p53 gene, but this mutation was not present in seven other tumors analyzed. No mutations were detected in codons 12/13 and 61 of the K-ras gene in any of the five tumors analyzed. Our findings suggest that K-ras overexpression is a rare alteration, whereas p53 protein overexpression (sometimes associated with mutated p53 gene), as assessed with the CM5 antibody, is a relatively common phenomenon in hot particle-induced preneoplastic and neoplastic rat lung lesions.     

Overexpression of the tumor-suppressor gene p53 in human ovarian tumor-tissues and its correlation with clinical stage

An extensive series of histological sections from various types of benign, borderline, and malignant human ovarian tumors were examined for expression of the p53 protein by immunohistochemical staining, using a new anti-p53 mouse monoclonal antibody. Positive staining for p53 was detected in 34% of all malignant ovarian cancer tissues. A high rate of positivity was observed in serous cystadenocarcinoma (59.7%). None of the borderline or benign tumors showed any reaction. No relation was observed between clinical stage, and the frequency of p53 positivity. Mutation of the p53 gene with overexpression of the mutant protein appears to be a specific genetic change in human ovarian cancer.     

利用组织芯片技术研究胃癌及其癌前病变中Bax、p53、Survivin表达的关系及意义

Objective： To explore the relationship between expressions of apoptosis-related protein Bax, Survivin and p53 and the molecular mechanisms of carcinogenesis and progression of gastric carcinoma. Methods： Tissue microarray and immunohistochemistry were used in this study. Results： The positive rate of Bax protein in gastric cancer （17.7%, 17/96） was significantly lower than those in adjacent normal mucosa （51%）, intestinal metaplasia （69.2%） and dysplasia （75%）, P 〈 0.01. The positive rate of Survivin expression in gastric cancer （80.6%, 89/98） was significantly higher than that in adjacent normal mucosa （3.9%）, P 〈 0.01. The positive rates of Survivin expression in tumors with different organ metastases （in lymph node metastasis 86.2%, liver 100% and ovarian 100%） were statistically higher than in tumors without metastasis （64.3%）, P 〈 0.05. Bax expression was correlated with Survivin but not with rap53 that was closely related to Survivin expression （P 〈 0.05） in gastric cancer. Conclusion： The abnormal expressions of Bax, Survivin and rap53 were correlated with the tumorigenesis and progression of gastric carcinoma. P53 and Survivin genes may share the similar mechanism in regulating cell apoptosis, and because of the mutation, p53 gene may lower its down-regulation to Survivin expression.     

Small subgroup of aggressive, highly proliferative prostatic carcinomas defined by p53 accumulation.

BACKGROUND: Mutations in the p53 gene resulting in the accumulation of altered p53 proteins with prolonged half-life have been found in a large variety of human malignancies. PURPOSE: We studied the significance of p53 protein accumulation in prostatic carcinoma. METHODS: The material consisted of 137 paraffin-embedded, primary prostatic carcinomas. Accumulation of p53 protein was studied by immunohistochemical staining using a polyclonal p53-specific CM-1 antibody. Proliferation activity was determined by DNA flow cytometry and by immunohistochemical detection of proliferative cell nuclear antigen (PCNA) using a monoclonal PC10 antibody. RESULTS: Eight (6%) of the tumors showed intense p53 staining in more than 20% of the tumor cells, 15 (11%) had only lower level immunoreactivity, and 114 (83%) showed no staining. High-level p53 accumulation was associated with high histologic grade (P less than .001), DNA aneuploidy (P less than .05), and high cell proliferation rate as defined by flow cytometric S-phase analysis (P less than .01) or PCNA expression (P less than .01). High-level p53 accumulation predicted short, progression-free interval (P less than .01) and poor survival (P less than .001), with about a 12-fold relative risk of death as compared with p53-negative cases. Low-level p53 accumulation had no prognostic significance. CONCLUSIONS: Accumulation of p53 confers proliferative advantage for prostatic carcinoma cells and defines a small subgroup of highly malignant carcinomas.     

CDKN2基因产物表达与卵巢癌生物学行为和预后的关系

为了解ＣＤＫＮ２基因与卵巢癌发生、生物学行为和预后的关系，采用ＳＰ法免疫组织化学染色观察了该基因产物ｐ１６蛋白在卵巢癌的表达情况。发现卵巢癌中ｐ１６蛋白的阳性率低于正常卵巢、良性和交界性肿瘤（Ｐ＜０．０１）。不同组织类型和不同分化程度卵巢癌之间ｐ１６蛋白的阳性率无显著差别（Ｐ＞０．０５），Ⅰ～Ⅱ期癌的阳性率高于Ⅲ～Ⅳ期癌（Ｐ＜０．０５），ｐ１６蛋白阴性的卵巢癌患者，其累积生存率低于ｐ１６蛋白阳性者（Ｐ＜０．０１）。结果表明，ＣＤＫＮ２基因失活与卵巢癌的发生有关，ｐ１６蛋白表达缺失与卵巢癌进展和预后不良有关。     

乳腺良恶性疾病端粒酶hTERT及调亡相关蛋白的表达

Objective： To analyse the expression of telomerase and apoptosis related protein, and explore the possible mechanism of breast cancer development. Methods： Immunohistochemistry method （SP） was used to detect the expression of hTERT, p53 and bcl-2 in the tissues of 48 cases of human breast cancer and 42 cases of benign lesions in breast. Results： The positive rates of expression of hTERT, p53 and bcl-2 in breast cancer were 87.50%, 56.25% and 54.17%, respectively. Compared with the groups of adjacent noncancerous and benign lesions, there was a significant difference among three types of tissues （P 〈 0.05）. The positive rates of expression of p53 and bcl-2 in the group with positive expression of hTERT were 64.28% and 61.90%, respectively, and their difference was significant compared with the negative group （P 〈 0.05）. Conclusion： There is a correlation between the activation of telomerases and p53 gene mutation in the development of breast cancer, and they are perhaps relation to the down regulation of bcl-2.     

Promoter hypermethylation profile of ovarian epithelial neoplasms.

PURPOSE: Ovarian carcinomas are believed to arise de novo from surface epithelium, but the actual molecular pathogenesis is unknown. The aim of this study was to compare the promoter hypermethylation profiles of ovarian epithelial neoplasms to better understand the role of epigenetic silencing in carcinogenesis. EXPERIMENTAL DESIGN: We analyzed the DNA promoter methylation status of eight tumor suppressor and cancer-related genes (p16, RARbeta, E-cadherin,H-cadherin, APC, GSTP1, MGMT, RASSF1A) in 23 benign cystadenomas, 23 low malignant potential (LMP) tumors, and 23 invasive carcinomas by methylation-specific PCR. RESULTS: Benign cystadenomas exhibited promoter hypermethylation in only two genes, p16 (13%) and E-cadherin (13%). LMP tumors also showed p16 (22%) and E-cadherin (17%) methylation, in addition to RARbeta (9%) and H-cadherin (4%). All eight genes were hypermethylated in invasive cancers at a frequency of 9% to 30%. The mean methylation index was highest in invasive tumors [0.20 versus 0.065 (LMP) and 0.033 (cystadenomas); P = 0.001]. Promoter methylation of at least one gene was most commonly observed among invasive cancers [78% versus 44% (LMP; P = 0.03) and 26% (cystadenomas; P = 0.0009)]. Three genes exhibited higher methylation frequencies in invasive tumors: RASSF1A (30% versus 0%; P = 0.0002), H-cadherin (22% versus 2%; P = 0.013), and APC (22% versus 0%; P = 0.003). CONCLUSIONS: Promoter hypermethylation is a frequent epigenetic event that occurs most commonly in invasive epithelial ovarian carcinomas. The profile of aberrant methylation suggests that an accumulation of events at specific genes may trigger malignant transformation of some benign cystadenomas and LMP tumors.