Using a Panel of Immunohistochemical Stains to Determine Risk of Lymph Node Metastases in Women with Endometrioid Adenocarcinoma of the Endometrium

Karina Zapiecki, Greg A. Miller, Zhen Zhou, Kelly J. Manahan, John P. Geisler

.

DOI: 10.4236/jct.2011.24067                

Abstract

Objectives: The purpose of this study was to determine whether a correlation exists between a panel of immunohistochemical stains (consisting of estrogen receptor (ER), progesterone receptor (PR) and wild type p53 (p53)) and nodal status in women with endometrioid endometrial cancer. Methods: Three hundred forty-three women underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, bilateral pelvic and para-aortic lymph node dissection performed. All tumors were stained for ER, PR and p53. This panel was compared to the patient’s nodal status and other clinic-pathologic factors. All data was collected from the patients’ charts. Results: One hundred eight patients had grade 1 tumors (83.3% node negative), one hundred forty three had grade 2 (86.6% node negative), and seventy had grade 3 (74.3% node negative). One hundred thirty six patients (39.6%) had tumors that were positive for ER, PR and negative for p53. Twenty eight patients (8.1%) had tumors that were negative for ER, PR and positive for p53. One hundred seventy nine patients (52.1%) had tumors that had mixed staining. Only 6 (4.4%) patients with ER+, PR+, p53– tumors had positive node nodes (P = 0.005). None of the sixty patients with grade 1 tumors that stained ER+, PR+, p53– had positive nodes found. Conclusion: In women with grade 1 disease, no positive nodes were found if the tumors stained positively for ER and PR and negatively for p53. Further studies will look at staining in diagnostic biopsies specimens and their correlation with nodal status.

Keywords

Correlation, Estrogen Receptor, Progesterone Receptor, p53, Endometrial Cancer, Nodes

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	M. J. Horner, L. A. G. Ries, M. Krapcho, N. Neyman, R. Aminou, N. Howlader, S. F. Altekruse, E. J. Feuer, L. Huang, A. Mariotto, B. A. Miller, D. R. Lewis, M. P. Eisner, D. G. Stinchcomb and B. K. Edwards (Eds.), SEER Cancer Statistics Review, National Cancer Institute, 1975-2006.
[2]	A. Jemal, R. Siegel, J. Xu and E. Ward, “Cancer Statistics,” CA: A Cancer Journal for Clinicians, Vol. 60, No. 5, 2010, pp. 277-300. doi:10.3322/caac.20073
[3]	A. B. Olawaiye and D. M. Boruta II, “Management of Women with Clear Cell Endometrial Cancer: A Society of Gynecologic Oncology (SGO) Review,” Gynecologic Oncology, Vol. 113, No. 2, 2009, pp. 277-283. doi:10.1016/j.ygyno.2009.02.003
[4]	K. May, A. Bryant, H. O. Dickinson, S. Kehoe and J. Morrison, “Lymphadenectomy for the Management of Endometrial Cancer,” Cochrane Database of Systematic Reviews, Vol. 20, No. 1, 2010, CD007585.
[5]	N. Yaegashi, K. Ito and H. Niikura, “Lymphadenectomy for Endometrial Cancer: Is Paraaortic Lymphadenectomy Necessary?” International Journal of Clinical Oncology, Vol. 12, No. 3, 2007, pp. 176-180. doi:10.1007/s10147-006-0621-2
[6]	J. P. Geisler, G. C. Linnemeier and K. J. Manahan, “Pelvic and Para-Aortic Lymphadenectomy in Patients with Endometrioid Adenocarcinoma of the Endometrium,” International Journal of Gynecology & Obstetrics, Vol. 98, No. 1, 2007, pp. 39-43. doi:10.1016/j.ijgo.2007.03.035
[7]	N. Sirisabya, T. Manchana, P. Worasethsin, N. Khemapech, R. Lertkhachonsuk, T. Sittisomwong, A. Vasuratna, W. Termrungruanglert and D. Tresukosol, “Is Complete Surgical Staging Necessary in Clinically Early-Stage Endometrial Carcinoma?” International Journal of Gynecological Cancer, Vol. 19, No. 6, 2009, pp. 1057-1061. doi:10.1111/IGC.0b013e3181a8ba85
[8]	D. S. Mohan, M. A. Samuels, M. A. Selim, A. D. Shalodi, R. J. Ellis, J. R. Samuels and H. J. Yun, “Long-Term Outcomes of Therapeutic Pelvic Lymphadenectomy for Stage I Endometrial Adenocarcinoma,” Gynecologic Oncology, Vol. 70, No. 2, 1998, pp. 165-171. doi:10.1006/gyno.1998.5098
[9]	C. V. Lutman, L. J. Havrilesky, J. M. Cragun, A. A. Secord, B. Calingaert, A. Berchuck, D. L. Clarke-Pearson and J. T. Soper, “Pelvic lymph Node Count Is an Important Prognostic Variable for FIGO Stage I and II Endometrial Carcinoma with High-Risk Histology,” Gynecologic Oncology, Vol. 102, No. 1, 2006, pp. 92-97. doi:10.1016/j.ygyno.2005.11.032
[10]	ASTEC study group, H. Kitchener, A. M. Swart, Q. Qian, C. Amos and M. K. Parmar, “Efficacy of Systematic Pelvic Lymphadenectomy in Endometrial Cancer (MRC ASTEC Trial): A Randomised Study,” Lancet, Vol. 373, No. 9658, 2009, pp. 125-136. doi:10.1016/S0140-6736(08)61766-3
[11]	M. Jovicic-Milentijevic, R. Ilic, V. Katic and V. Zivkovic, “Correlation of Steroid Hormone Receptor Status with Histological and Nuclear Grading in Breast Carcinoma,” Journal of Balkan Union of Oncology, Vol. 9, No. 2, 2004, pp. 173-177.
[12]	T. Tantivatana, M. Chongthanakorn, K. Rongsriyam and K. Katanyoo, “Treatment Outcomes and Prognostic Factors of Patients with Breast Cancer: A Retrospective Review,” Journal of the Medical Association of Thailand, Vol. 92, No. 8, 2009, pp. 1084-1093.
[13]	S. Liu, S. K. Chia, E. Mehl, S. Leung, A. Rajput, M. C. Cheang and T. O. Nielsen, “Progesterone Receptor Is a Significant Factor Associated with Clinical Outcomes and Effect of Adjuvant Tamoxifen Therapy in Breast Cancer Patients,” Breast Cancer Research and Treatment, Vol. 119, No. 1, 2010, pp. 53-61. doi:10.1007/s10549-009-0318-0
[14]	J. M. Cragun, L. J. Havrilesky, B. Calingaert, I. Synan, A. A. Secord, J. T. Soper, D. L. Clarke-Pearson and A. Berchuck, “Retrospective Analysis of Selective Lymphadenectomy in Apparent Early-Stage Endometrial Cancer,” Journal of Clinical Oncology, Vol. 23, No. 16, 2005, pp. 3668-3675. doi:10.1200/JCO.2005.04.144
[15]	S. J. Payne, R. L. Bowen, J. L. Jones and C. A. Wells, “Predictive Markers in Breast Cancer—the Present,” Histopathology, Vol. 52, No. 1, 2008, pp. 82-90. doi:10.1111/j.1365-2559.2007.02897.x
[16]	H. Arias-Pulido, H. O. Smith, N. E. Joste, T. Bocklage, C. R. Qualls, A. Chavez, E. R. Prossnitz and C. F. Verschraegen, “Estrogen and Progesterone Receptor Status and Outcome in Epithelial Ovarian Cancers and Low Malignant Potential Tumors,” Gynecologic Oncology, Vol. 114, No. 3, 2009, pp. 480-485. doi:10.1016/j.ygyno.2009.05.045
[17]	Y. Todo, H. Kato, M. Kaneuchi, H. Watari, M. Takeda and N. Sakuragi, “Survival Effect of Para-Aortic Lymphadenectomy in Endometrial Cancer (SEPAL Study): A Retrospective Cohort Analysis,” Lancet, Vol. 376, 2010, pp. 1165-1172. doi:10.1016/S0140-6736(09)62002-X
[18]	E. Sivridis, A. Giatromanolaki, M. Koukourakis and P. Anastasiadis, “Endometrial Carcinoma: Association of Steroid Hormone Receptor Expression with Low Angiogenesis and Bcl-2 Expression,” Virchows Arch, Vol. 438, No. 5, 2001, pp. 470-477. doi:10.1007/s004280000361
[19]	S. Kounelis, N. Kapranos, E. Kouri, D. Coppola, H. Papadaki and M. W. Jones, “Immunohistochemical Profile of Endometrial Adenocarcinoma: A Study of 61 Cases and Review of the Literature,” Modern Pathology, Vol. 13, No. 4, 2000, pp. 379-388. doi:10.1038/modpathol.3880062
[20]	C. Suthipintawong, C. Wejaranayang and C. Vipupinyo, “Prognostic Significance of ER, PR, Ki67, C-erbB-2, and p53 in Endometrial Carcinoma,” Journal of the Medical Association of Thailand, Vol. 91, 2008, pp. 1779-1784.
[21]	K. S. McCarty Jr., T. K. Barton, B. F. Fetter, W. T. Creasman and K. S. McCarty Sr., “Correlation of Estrogen and Progesterone Receptors with Histologic Differentiation in Endometrial Adenocarcinoma,” American Journal of Pathology, Vol. 96, No. 1, 1979, pp. 171-183.
[22]	V. C. Jordan and A. M. Brodie, “Development and Evolution of Therapies Targeted to the Estrogen Receptor for the Treatment and Prevention of Breast Cancer,” Steroids, Vol. 72, No. 1, 2007, pp. 7-25. doi:10.1016/j.steroids.2006.10.009
[23]	S. L. Harris and A. J. Levine, “The p53 Pathway: Positive and Negative Feedback Loops,” Oncogene, Vol. 24, 2005, pp. 2899-2908. doi:10.1038/sj.onc.1208615
[24]	V. H. Jongen, J. M. Briet, R. A. de Jong, E. Joppe, K. A. ten Hoor, H. M. Boezen, D. B. Evans, H. Hollema, A. G. van der Zee and H. W. Nijman, “Aromatase, Cyclooxygenase 2, HER-2/Neu, and p53 as Prognostic Factors in Endometrioid Endometrial Cancer,” International Journal of Gynecological Cancer, Vol. 19, No. 4, 2009, pp. 670-676. doi:10.1111/IGC.0b013e3181a47c25
[25]	C. Suthipintawong, C. Wejaranayang and C. Vipupinyo, “Prognostic Significance of ER, PR, Ki67, C-erbB-2, and p53 in Endometrial Carcinoma,” Journal of the Medical Association of Thailand, Vol. 91, 2008, pp. 1779-1784.
[26]	J. P. Geisler, H. E. Geisler, M. C. Wiemann, Z. Zhou, G. A. Miller and W. Crabtree, “p53 Expression as a Prognostic Indicator of 5-year Survival in Endometrial Cancer,” Gynecologic Oncology, Vol. 74, No. 3, 1999, pp. 468-471. doi:10.1006/gyno.1999.5482
[27]	M. L. Appel, M. I. Edelweiss, J. Fleck, L. F. Rivero, W. A. Rivoire, H. I. Monego and R. Dos Reis, “p53 and BCL-2 as Prognostic Markers in Endometrial Carcinoma,” Pathology & Oncology Research, Vol. 14, No. 1, 2008, pp. 23-30. doi:10.1007/s12253-008-9000-9
[28]	I. Kalogiannidis, M. Bobos, A. Papanikolaou, A. Makedos, I. Amplianitis, I. Vergote, E. Nenopoulou and G. Makedos, “Immunohistochemical Bcl-2 Expression, p53 Overexpression, PR and ER Status in Endometrial Carcinoma and Survival Outcomes,” European Journal of Gynaecological Oncology, Vol. 29, 2008, pp. 19-25.
[29]	A. Alkushi, P. Lim, A. Coldman, D. Huntsman, D. Miller and C. B. Gilks, “Interpretation of p53 Immunoreactivity in Endometrial Carcinoma: Establishing a Clinically Relevant Cut-Off Level,” International Journal of Gynecological Pathology, Vol. 23, No. 2, 2004, pp. 129-137. doi:10.1097/00004347-200404000-00007
[30]	E. L. Trimble, C. Kosary and R. C. Park, “Lymph Node Sampling and Survival in Endometrial Cancer,” Gynecologic Oncology, Vol. 71, No. 3, 1998, pp. 340-343. doi:10.1006/gyno.1998.5254
[31]	D. C. Smith, O. K. Macdonald, C. M. Lee and D. K. Gaffney, “Survival Impact of Lymph Node Dissection in Endometrial Adenocarcinoma: A Surveillance, Epidemiology, and End Results Analysis,” International Journal of Gynecological Cancer, Vol. 18, No. 2, 2008, pp. 255-261. doi:10.1111/j.1525-1438.2007.01020.x
[32]	J. K. Chan, M. K. Cheung, W. K. Huh, K. Osann, A. Husain, N. N. Teng and D. S. Kapp, “Therapeutic Role of Lymph Node Resection in Endometrioid Corpus Cancer: A Study of 12,333 Patients,” Cancer, Vol. 107, No. 8, 2006, pp. 1823-1830. doi:10.1002/cncr.22185
[33]	C. V. Lutman, L. J. Havrilesky, J. M. Cragun, A. A. Secord, B. Calingaert, A. Berchuck, D. L. Clarke-Pearson and J. T. Soper, “Pelvic Lymph Node Count Is an Important Prognostic Variable for FIGO Stage I and II Endometrial Carcinoma with High-Risk Histology,” Gynecologic Oncology, Vol. 102, No. 1, 2006, pp. 92-97.