CEBP CTRC-AACR San Antonio Breast Cancer Symposium Cancer Health Disparities Conference 2009
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jeon, Y.-T.
Right arrow Articles by Song, Y.-S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jeon, Y.-T.
Right arrow Articles by Song, Y.-S.
Cancer Epidemiology Biomarkers & Prevention Vol. 13, 1538-1542, September 2004
© 2004 American Association for Cancer Research

Short Communication

Cyclooxygenase-2 and p53 Expressions in Endometrial Cancer

Yong-Tark Jeon1,4, Sokbom Kang1,4, Dae-Hee Kang2, Keun-Young Yoo2, In-Ae Park3, Yung-Jue Bang4, Jae Weon Kim1,4, Noh-Hyun Park1,4, Soon-Beom Kang1,4, Hyo-Pyo Lee1,4 and Yong-Sang Song1,4

Departments of 1 Obstetrics and Gynecology, 2 Preventive Medicine, and 3 Pathology and 4 Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea

Requests for reprints: Yong-Sang Song, Department of Obstetrics and Gynecology, College of Medicine, Seoul National University, 28 Yongun-dong, Jongno-gu, Seoul 110-744, Korea. Phone: 82-2-760-2822; Fax: 82-2-762-3599. E-mail: yssong{at}snu.ac.kr


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Cyclooxygenase-2 (COX-2) has been known to be related with various types of carcinoma, but we have insufficient knowledge about the association between COX-2 and endometrial cancer. Many have reported a close relationship between p53 expression and a poor prognosis in endometrial cancer, but it is unclear whether p53 is an independent prognostic factor. To clarify these uncertainties, we examined the expressions of COX-2 and p53 in endometrial cancer tissues. The study was carried on 152 endometrial cancer patients who had operation at Seoul National University Hospital. Paraffin-embedded tissue blocks were sectioned and immunostained using monoclonal anti-COX-2 and anti-p53 antibodies. Twenty-seven (17.8%) specimens stained as COX-2 positive. COX-2 positivity was more frequently observed in postmenopausal patients than in premenopausal patients (8.8% versus 25.0%; P = 0.009). However, COX-2 positivity did not show a statistically significant association with any other clinicopathologic characteristic (parity, body mass index, histotype, International Federation of Gynecology and Obstetrics stage, grade, lymph node metastasis, deep myometrial invasion, or p53 overexpression). Thirty-one (20.4%) specimens showed p53 overexpression and this was significantly correlated with an advanced stage (P = 0.001), poor differentiation (P < 0.001), lymph node metastasis (P = 0.012), and deep myometrial invasion (P < 0.001). Multivariate Cox regression analysis showed that advanced stage was an independent prognostic factor of survival, but p53 overexpression was not. COX-2 may be associated with endometrial cancer carcinogenesis during the postmenopausal period but not with tumor aggressiveness and p53 overexpression. The p53 overexpression was found to be strongly associated with endometrial cancer aggressiveness.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Endometrial cancer is the most common malignancy of the female genital tract in developed countries and is expected to account for 6% of new cancer cases among women in the United States in 2003 (1). Korea has experienced a remarkable increase in endometrial cancer incidence, that is, 132 patients in 1991 and 581 patients in 2001 according to the tumor registry (2).

Recently, much attention has been focused on cyclooxygenase (COX), which is a rate-limiting enzyme in the biosynthesis of prostaglandins from arachidonic acid. Two isoforms of COX are known, COX-1 and COX-2, both of which participate in the formation of a variety of eicosanoids, including prostaglandins D2, E2, I2, and F2{alpha} and thromboxane A.

COX-2 is an inducible immediate-early gene, which is up-regulated by various stimuli, including mitogens, cytokines, growth factors, and tumor promoters (3). Several studies have shown that COX-2 expression is aberrantly increased in various human epithelial cancers, including those of colorectal, esophageal, gastric, lung, and bladder origin (4-9). These findings suggest that the cellular up-regulation of COX-2 may be a common mechanism in epithelial carcinogenesis. In addition, many studies have shown that COX-2 expression reduces apoptosis, increases the invasiveness of malignant cells, and promotes angiogenesis (10-15). To our knowledge, two reports are available on the expression of COX-2 and its possible clinical significance in patients with endometrial cancer (16, 17), but they have shown quite different results each other.

p53 is often called the cellular gatekeeper or as the guardian of the genome, and its importance is has been emphasized by the discovery of mutations in p53 in >50% of all human tumors. The nature of these genetic changes in cancer cells is most commonly a missense mutation in one allele, producing a faulty protein that is observed at high concentrations in these cells followed by a reduction to homozygosity (18).

In endometrial cancer, mutations of the p53 tumor suppressor gene have been found in ~10% to 20% and more frequently in serous papillary and clear cell histologic types (19). Although the use of the immunohistochemical expression of p53 as an indication of the level of p53 mutation presents problems in terms of false positivity and negativity (20), many clinical correlated studies of p53 immunostaining have reported. The abnormal expression of p53 has been associated with an advanced stage and poor survival by several studies, although some have reported that the overexpression of p53 is not an independent prognostic factor in endometrial cancer (21-31). In addition, several reports suggested that p53 and COX-2 might have close relationship (32-34).

To clarify these uncertainties, in the present study, we examined the expressions of COX-2 and p53 in endometrial cancer and their relationships with clinicopathologic characteristics.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
This study included 152 endometrial cancer patients with archived paraffin-embedded tissue blocks. All patients were admitted, treated, and followed up at the Department of Obstetrics and Gynecology, Seoul National University Hospital. Mean patients' age was 50.9 years (range 26–76 years), and no patient had history of regular drug ingestion such as nonsteroidal anti-inflammatory drugs or COX-2 inhibitors. Staging was done according to the 1988 International Federation of Gynecology and Obstetrics classification: stage I, n = 112 (73.7%); stage II, n = 13 (8.6%); stage III, n = 18 (11.8%); and stage IV, n = 9 (5.9%). Two to 3 weeks after staging laparotomy, all the patients, except stage Ia with grade 1 or 2, received a radiation therapy. Patients with stage IV disease had six or more cycles of cisplatin-based chemotherapy after radiation. As of August 2003, the median follow-up period was 33.5 months (range 1–124 months). During the follow-up period, nine died of the disease and eight experienced disease recurrence. Of those that experienced recurrence, four died of the disease and four were alive with disease.

Immunohistochemical staining was done as described previously (14, 15) using the following primary antibodies: COX-2 (mouse monoclonal, clone 33, 1:50 dilution, Transduction Laboratories, Lexington, KY), and p53 (mouse monoclonal, clone DO-7, 1:50 dilution, DAKO A/S, Copenhagen, Denmark).

A specialized pathologist blind to the patients' clinical features reviewed slides and quantified the immunohistochemical data. The percentage of cells expressing COX-2 was estimated by dividing the number of positively stained tumor cells by the total number of tumor cells. For COX-2 expression, if 5% (median value) or more tumor cells were stained, the sample was defined as positive. For p53 overexpression, when there were at least 10% (median value) of tumor cells stained, it was considered as positive.

Statistical analyses were carried out using SPSS for Windows version 10.0.5 (SPSS Inc., Chicago, IL). The association of variables was evaluated by the {chi}2 test or the t test if applicable. Log rank test and multivariate analysis with Cox regression were used for survival analysis. P < 0.05 was considered statistically significant.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
COX-2 immunoreactivity of normal endometrial gland and stroma was minimal irrespective of menstrual phase (proliferative or secretory). In contrast, tumor cells showed significant immunoreactivity for COX-2. Of the 152 specimens, 27 (17.8%) were COX-2 positive. Patients showing COX-2 positivity were older and more frequently postmenopausal than those showing COX-2 negativity (P = 0.009). However, COX-2 positivity was not found to show a statistically significant association with any other clinicopathologic characteristic or p53 overexpression (Table 1).


View this table:
[in this window]
[in a new window]
  		Table 1. Clinicopathologic characteristics according to COX-2 expression

 
Thirty-one (20.4%) specimens showed p53 overexpression, and this was significantly associated with advanced stage (stage III or IV; P = 0.001), poor differentiation (grade 2 or 3; P < 0.001), lymph node metastasis (P = 0.012), and deep myometrial invasion (P < 0.001; Table 2).


View this table:
[in this window]
[in a new window]
  		Table 2. Clinicopathologic characteristics according to p53 overexpression

 
Log rank test showed that old age (≥65 years; P = 0.02), advanced stage (P < 0.001), poor differentiation (grade 2 or 3; P < 0.001), lymph node metastasis (P < 0.001), deep myometrial invasion (P < 0.001), and p53 overexpression (P < 0.001) were related to patient survival. All the covariates mentioned above and COX-2 were included in multivariate Cox regression analysis, and it showed that advanced stage was an independent prognostic factor of survival but not p53 overexpression (Table 3).


View this table:
[in this window]
[in a new window]
  		Table 3. Hazard ratios by multivariate Cox regression analysis

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
In this study, high COX-2 expression was observed more frequently in postmenopausal patients than premenopausal women with endometrial cancer. Although the exact cause of this difference is unknown, it can be supposed that endometrial cancer arising from the postmenopausal endometrium may have quite a different regulatory system of COX-2 or may use the COX-2 gene more frequently than a cancer from the perimenopausal or normal cyclic endometrium. This postulation corresponds well with the long-standing knowledge that there are two different pathogenetic types of endometrial cancer. The most common type occurs in younger, perimenopausal women with a history of exposure to unopposed estrogen, either endogenous or exogenous. The other type of endometrial cancer occurs in women with no source of estrogen stimulation of the endometrium (35). Therefore, this study may provide a molecular basis on the genesis of two different pathogenetic types of endometrial cancer and may be grounds for further studies on the preventive effect of nonsteroidal anti-inflammatory drugs or COX-2 inhibitors on endometrial cancer as it occurs in postmenopausal women.

As commented in Introduction, two studies on COX-2 expression and clinical significance in endometrial cancer showed quite different results each other. Fujiwaki et al. (16) analyzed 63 patients with endometrial cancer and found that COX-2 immunoreactivity did not correlate with any clinical variables (menopausal status, International Federation of Gynecology and Obstetrics stage, histologic type, tumor size, histologic grade, or myometrial invasion) or with prognosis. Ferrandina et al. (17) studied 69 patients with endometrial cancer in Italy and reported that COX-2 positivity was higher in endometrial cancer with cervical or extrauterine involvement than in tumors limited to the corpus. They also found that COX-2 positivity gradually increased from grade 1 to grade 3 endometrial carcinoma, and COX-2 positive patients tended to have shorter disease-free survivals than COX-2-negative patients, although this was not statistically significant. The cause of the disagreement between these two studies is unknown, but it may have been due to the technical differences, such as different antibodies and/or quantification of staining. Another explanation for the discrepancy can be a racial or regional differences of the study population (Japanese versus Italian). In addition, although different from the Japanese study in the antibody type used, the proportion of the menopausal women, and the criteria for COX-2 positivity, the present study on Korean women shows very similar results with that on Japanese but not with that on Italian. This might suggest the racial difference in endometrial carcinogenesis such as the role of COX-2 in carcinogenesis and progression.

Although the close relationship between the expressions of COX-2 and p53 was reported in several studies (32-34), it remains unknown that why there was no relation in this study. This may suggest the possibility of tissue-specific modulation of COX-2 gene regulation.

There is the substantial debate as to whether p53 overexpression is an independent prognostic factor in endometrial cancer. As shown by the work of Lundgren et al. (30) and Erdem et al. (31), we found that p53 expression is not an independent prognostic factor. However, Lundgren et al. (30) did not include age, lymph node metastasis, and myometrial invasion depth as prognostic variables. Such differences prevent direct comparisons of these three studies, which showed similar results by multivariate analysis in terms of identifying independent prognostic factors of endometrial cancer. In the previously mentioned studies (21-31), diverse antibodies were used against p53 and different criteria were used for p53 positivity. However, the overexpression of p53 protein was found to be associated with advanced stage, poor differentiation, lymph node metastasis, and deep myometrial invasion in the current study, and this corresponded well with the findings of other studies (24, 36, 37).

Many have reported that p53 mutation or immunostaining is significantly higher in papillary serous than in endometrioid carcinomas (38-44). In the present study, no significant association was found between p53 overexpression and nonendometrioid carcinoma. The relatively small number of nonendometrioid carcinomas (only five cases) in the study may be a cause. However, nonendometrioid carcinoma showed a trend toward more frequent p53 overexpression.

In conclusion, COX-2 may be associated with the carcinogenesis of endometrial cancer during the postmenopausal period but not with tumor aggressiveness and p53. Moreover, the COX-2 expression in endometrial cancer may be influenced by ethnicity. In addition, this study shows that p53 expression is strongly associated with the aggressiveness of endometrial cancer but not an independent prognostic factor of survival.


   Footnotes
 
Grant support: Republic of Korea Ministry of Health and Welfare grant 01-PJ1-PG1-01CH05-0001.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 2/ 3/04; revised 4/ 7/04; accepted 4/15/04.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Jemal A, Murray T, Samuels A, Ghafoor A, Ward E, Thun MJ. Cancer statistics, 2003. CA Cancer J Clin 2003;53:5–26.[Abstract/Free Full Text]
  2. Department of Gynecologic Tumor, Korean Society of Obstetrics and Gynecology. Annual report of gynecologic cancer registry program in Korea for 2001. Korean J Obstet Gynecol 2003;46:1849–87.
  3. Williams CS, DuBois RN. Prostaglandin endoperoxide synthase: why two isoforms? Am J Physiol 1996;270:G393–400.
  4. Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrenbach S, DuBois RN. Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 1994;107:1183–8.[Medline]
  5. Hao X, Bishop AE, Wallace M, et al. Early expression of cyclooxygenase-2 during sporadic colorectal carcinogenesis. J Pathol 1999;187:295–301.[CrossRef][Medline]
  6. Wilson KT, Fu S, Ramanujam KS, Meltzer SJ. Increased expression of inducible nitric oxide synthase and cyclooxygenase-2 in Barrett's esophagus and associated adenocarcinomas. Cancer Res 1998;58:2929–34.[Abstract/Free Full Text]
  7. Ristimaki A, Honkanen N, Jankala H, Sipponen P, Harkonen M. Expression of cyclooxygenase-2 in human gastric carcinoma. Cancer Res 1997;57:1276–80.[Abstract/Free Full Text]
  8. Wolff H, Saukkonen K, Anttila S, Karjalainen A, Vainio H, Ristimaki A. Expression of cyclooxygenase-2 in human lung carcinoma. Cancer Res 1998;58:4997–5001.[Abstract/Free Full Text]
  9. Mohammed SI, Knapp DW, Bostwick DG, et al. Expression of cyclooxygenase-2 (COX-2) in human invasive transitional cell carcinoma (TCC) of the urinary bladder. Cancer Res 1999;59:5647–50.[Abstract/Free Full Text]
  10. Tsujii M, DuBois RN. Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell 1995;83:493–501.[CrossRef][Medline]
  11. Tsujii M, Kawano S, DuBois RN. Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. Proc Natl Acad Sci USA 1997;94:3336–40.[Abstract/Free Full Text]
  12. Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois RN. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 1998;93:705–16.[CrossRef][Medline]
  13. Kim HJ, Wu HG, Park IA, Ha SW. High cyclooxygenase-2 expression is related with distant metastasis in cervical cancer treated with radiotherapy. Int J Radiat Oncol Biol Phys 2003;55:16–20.[CrossRef][Medline]
  14. Kim MH, Seo SS, Song YS, et al. Expression of cyclooxygenase-1 and -2 associated with expression of VEGF in primary cervical cancer and at metastatic lymph nodes. Gynecol Oncol 2003;90:83–90.[CrossRef][Medline]
  15. Seo SS, Song YS, Kang DH, et al. Expression of cyclooxygenase-2 in association with clinicopathological prognostic factors and molecular markers in epithelial ovarian cancer. Gynecol Oncol 2004;92:927–35.[CrossRef][Medline]
  16. Fujiwaki R, Iida K, Kanasaki H, Ozaki T, Hata K, Miyazaki K. Cyclooxygenase-2 expression in endometrial cancer: correlation with microvessel count and expression of vascular endothelial growth factor and thymidine phosphorylase. Hum Pathol 2002;33:213–9.[CrossRef][Medline]
  17. Ferrandina G, Legge F, Ranelletti FO, et al. Cyclooxygenase-2 expression in endometrial carcinoma: correlation with clinicopathologic parameters and clinical outcome. Cancer 2002;95:801–7.[CrossRef][Medline]
  18. Levine AJ. p53, the cellular gatekeeper for growth and division. Cell 1997;88:323–31.[CrossRef][Medline]
  19. Salvesen HB, Akslen LA. Molecular pathogenesis and prognostic factors in endometrial carcinoma. APMIS 2002;110:673–89.[CrossRef][Medline]
  20. Battifora H. p53 Immunohistochemistry: a word of caution. Hum Pathol 1994;25:435–7.[CrossRef][Medline]
  21. Pisani AL, Barbuto DA, Chen D, Ramos L, Lagasse LD, Karlan BY. HER-2/neu, p53, and DNA analyses as prognosticators for survival in endometrial carcinoma. Obstet Gynecol 1995;85:729–34.[Abstract]
  22. Soong R, Knowles S, Williams KE, Hammond IG, Wysocki SJ, Iacopetta BJ. Overexpression of p53 protein is an independent prognostic indicator in human endometrial carcinoma. Br J Cancer 1996;74:562–7.[Medline]
  23. Geisler JP, Geisler HE, Wiemann MC, Zhou Z, Miller GA, Crabtree W. p53 expression as a prognostic indicator of 5-year survival in endometrial cancer. Gynecol Oncol 1999;74:468–71.[CrossRef][Medline]
  24. Salvesen HB, Iversen OE, Akslen LA. Prognostic significance of angiogenesis and Ki-67, p53, and p21 expression: a population-based endometrial carcinoma study. J Clin Oncol 1999;17:1382–90.[Abstract/Free Full Text]
  25. Sung CJ, Zheng Y, Quddus MR, et al. p53 as a significant prognostic marker in endometrial carcinoma. Int J Gynecol Cancer 2000;10:119–27.[CrossRef][Medline]
  26. Ohkouchi T, Sakuragi N, Watari H, et al. Prognostic significance of Bcl-2, p53 overexpression, and lymph node metastasis in surgically staged endometrial carcinoma. Am J Obstet Gynecol 2002;187:353–9.[CrossRef][Medline]
  27. Lukes AS, Kohler MF, Pieper CF, et al. Multivariable analysis of DNA ploidy, p53, and HER-2/neu as prognostic factors in endometrial cancer. Cancer 1994;73:2380–5.[CrossRef][Medline]
  28. Reinartz JJ, George E, Lindgren BR, Niehans GA. Expression of p53, transforming growth factor {alpha}, epidermal growth factor receptor, and c-erbB-2 in endometrial carcinoma and correlation with survival and known predictors of survival. Hum Pathol 1994;25:1075–83.[CrossRef][Medline]
  29. Nordstrom B, Strang P, Lindgren A, Bergstrom R, Tribukait B. Endometrial carcinoma: the prognostic impact of papillary serous carcinoma (UPSC) in relation to nuclear grade, DNA ploidy and p53 expression. Anticancer Res 1996;16:899–904.[Medline]
  30. Lundgren C, Auer G, Frankendal B, Moberger B, Nilsson B, Nordstrom B. Nuclear DNA content, proliferative activity, and p53 expression related to clinical and histopathologic features in endometrial carcinoma. Int J Gynecol Cancer 2002;12:110–8.[CrossRef][Medline]
  31. Erdem O, Erdem M, Dursun A, Akyol G, Erdem A. Angiogenesis, p53, and bcl-2 expression as prognostic indicators in endometrial cancer: comparison with traditional clinicopathologic variables. Int J Gynecol Pathol 2003;22:254–60.[CrossRef][Medline]
  32. Han JA, Kim JI, Ongusaha PP, et al. P53-mediated induction of COX-2 counteracts p53- or genotoxic stress-induced apoptosis. EMBO J 2002;21:5635–44.[CrossRef][Medline]
  33. Shun CT, Wu MS, Huang SP, Wang HP, Chuang SM, Lin JT. Cyclooxygenase-2 expression correlates with nuclear p53 accumulation in gastric carcinoma. Hepatogastroenterology 2003;50:988–92.[Medline]
  34. Gallo O, Schiavone N, Papucci L, et al. Down-regulation of nitric oxide synthase-2 and cyclooxygenase-2 pathways by p53 in squamous cell carcinoma. Am J Pathol 2003;163:723–32.[Abstract/Free Full Text]
  35. Berek JS, editor. Novak's gynecology. 13th ed. Philadelphia: Lippincott Williams & Wilkins; 2002. p. 1144.
  36. Berchuck A, Kohler MF, Marks JR, Wiseman R, Boyd J, Bast RC Jr. The p53 tumor suppressor gene frequently is altered in gynecologic cancers. Am J Obstet Gynecol 1994;170:246–52.[Medline]
  37. Taskin M, Lallas TA, Barber HR, Shevchuk MM. bcl-2 and p53 in endometrial adenocarcinoma. Mod Pathol 1997;10:728–34.[Medline]
  38. Sherman ME, Bur ME, Kurman RJ. p53 in endometrial cancer and its putative precursors: evidence for diverse pathways of tumorigenesis. Hum Pathol 1995;26:1268–74.[CrossRef][Medline]
  39. Soslow RA, Shen PU, Chung MH, Isacson C. Distinctive p53 and mdm2 immunohistochemical expression profiles suggest different pathogenetic pathways in poorly differentiated endometrial carcinoma. Int J Gynecol Pathol 1998;17:129–34.[Medline]
  40. Tashiro H, Isacson C, Levine R, Kurman RJ, Cho KR, Hedrick L. p53 gene mutations are common in uterine serous carcinoma and occur early in their pathogenesis. Am J Pathol 1997;150:177–85.[Abstract]
  41. Moll UM, Chalas E, Auguste M, Meaney D, Chumas J. Uterine papillary serous carcinoma evolves via a p53-driven pathway. Hum Pathol 1996;27:1295–300.[CrossRef][Medline]
  42. Bur ME, Perlman C, Edelmann L, Fey E, Rose PG. p53 expression in neoplasms of the uterine corpus. Am J Clin Pathol 1992;98:81–7.[Medline]
  43. Inoue M, Okayama A, Fujita M, et al. Clinicopathological characteristics of p53 overexpression in endometrial cancers. Int J Cancer 1994;58:14–9.[Medline]
  44. Halperin R, Zehavi S, Habler L, Hadas E, Bukovsky I, Schneider D. Comparative immunohistochemical study of endometrioid and serous papillary carcinoma of endometrium. Eur J Gynaecol Oncol 2001;22:122–6.[Medline]



This article has been cited by other articles:


Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
F. Modugno, R. B. Ness, C. Chen, and N. S. Weiss
Inflammation and Endometrial Cancer: A Hypothesis
Cancer Epidemiol. Biomarkers Prev., December 1, 2005; 14(12): 2840 - 2847.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jeon, Y.-T.
Right arrow Articles by Song, Y.-S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jeon, Y.-T.
Right arrow Articles by Song, Y.-S.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online