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Journal of Cancer Prevention

Original Article

Journal of Cancer Prevention -0001; 19(3): 231-239

Published online November 30, -0001

https://doi.org/10.15430/JCP.2014.19.3.231

© Korean Society of Cancer Prevention

L1 Cell Adhesion Molecule Expression Is Associated With Pelvic Lymph Node Metastasis and Advanced Stage in Diabetic Patients With Endometrial Cancer: A Matched Case Control Study

Dong Hoon Suh1, Min A Kim2, Hee Seung Kim3, Hyun Hoon Chung3, Noh Hyun Park3, Yong Sang Song3,4,5, and Soon-Beom Kang6

1Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Korea, 2Department of Pathology, Seoul National University College of Medicine, Seoul, Korea, 3Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea, 4Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea, 5Major in Biomodulation, World Class University, Seoul National University, Seoul, Korea, 6Women’s Gynecologic Oncology Center, Department of Obstetrics and Gynecology, Konkuk University School of Medicine, Seoul, Korea

Correspondence to :
Soon-Beom Kang, Department of Obstetrics and Gynecology, Konkuk University School of Medicine, 120-1 Neungdong-ro, Hwayang-dong, Gwangjin-gu, Seoul 143-729, Korea, Tel: +82-2-2030-8361, Fax: +82-2-2030-8363, E-mail: ksb308@gmail.com

Received: July 28, 2014; Revised: August 31, 2014; Accepted: September 1, 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Background:

Diabetic patients with endometrial cancer had more lymph node metastasis than non-diabetic patients with endometrial cancer. L1 cell adhesion molecule (L1CAM) could be possibly associated with lymph node metastasis in diabetic patients with endometrial cancer via epithelial-mesenchymal transition. We aimed to investigate the association between L1CAM expression and lymph node metastasis in diabetic patients with endometrial cancer.


Methods:

We conducted a matched case control study of 68 endometrial cancer patients who comprise each 34 diabetic and non-diabetic patients. L1CAM expression was evaluated by immunohistochemistry using fresh formalin-fixed paraffin-embedded tissue block of the patients. The association between L1CAM expression and pelvic lymph node metastasis was assessed according to the presence of diabetes.


Results:

Of the 68 patients, 13 (19.1%) were positive for L1CAM immunostaining. Positive rate of L1CAM expression in diabetic endometrial cancer patients was similar to that in non-diabetic endometrial cancer patients (14.7% vs. 23.5%, P = 0.355). Tumor recurred more frequently in patients with positive L1CAM expression than those with negative L1CAM expression (33.3% vs. 1.6%, P = 0.019). However, we failed to find any significant association between L1CAM expression and lymph node metastasis. Only for the diabetic patients (n = 34), patients with pelvic lymph node metastasis had more L1CAM expression than those without lymph node metastasis (50.0% vs. 3.6%, P = 0.035). Advanced stage was the only risk factor for recurrence that showed a significant association with L1CAM expression for the diabetic endometrial cancer patients (P = 0.006), as well as all the enrolled patients (P = 0.014).


Conclusion:

L1CAM expression is associated with pelvic lymph node metastasis and advanced stage in diabetic patients with endometrial cancer.

Keywords: Neural cell adhesion molecule L1, Immunohistochemistry, Endometrial cancer, Diabetes mellitus, Lymphatic metastasis

INTRODUCTION

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Endometrial cancer (EC) is the most common gynecological malignancy in the United States.1 ECs commonly present in the early stage and almost two-thirds are diagnosed in stage I, according to the 2009 International Federation of Gynecology and Obstetrics (FIGO) staging system. However, once tumor recurs, treatment of recurrent EC remains a difficult clinical problem, due to the ineffectiveness of any combinations of chemotherapy, radiation therapy, and novel molecular targeted agents.1 Lymph node (LN) metastasis is one of the most important risk factors for recurrence of EC.2 Patients with pelvic and paraaortic LN metastasis are designated as FIGO stage IIIC1 and IIIC2, respectively.3

Diabetes mellitus (DM) is known to increase the risk of EC.4 Moreover, diabetic patients with EC were reported to have more LN metastasis and poorer prognosis than non-diabetic EC patients.5 Therefore, reliable pre-or intra-operative predictors for LN metastasis could help tailor the treatment and improve the prognosis, especially in diabetic patients with EC.

L1 cell adhesion molecule (L1CAM) is a type I membrane glycoprotein of the immunoglobulin superfamily, which is initially identified in the nervous system.6 Apart from multiple regulatory functions of L1CAM in neuronal cells, such as cell-to-cell interactions, neuronal migration, and neurite fasciculation and myelination,7 recent studies have demonstrated that L1CAM was aberrantly expressed in a variety of human cancers, including EC.8?10 Overexpression of L1CAM in tumor cells was reported to increase cell motility, enhance the growth rate, and promote cell transformation and tumorigenicity, as well as form metastases.6 High L1CAM expression was shown to be associated with recurrent disease and short survival in EC.11 However, there was no study that evaluated the association of L1CAM expression in EC with LN metastasis.

A mechanism how DM negatively affects the prognosis of EC remained to be determined. Based on a small number of studies, which provided indirect evidence for possible association of L1CAM expression with DM,12?14 we hypothesized that L1CAM expression might play a crucial role in LN metastasis in diabetic patients with EC. In this study, we aimed to investigate the association between L1CAM expression and LN metastasis in diabetic patients with EC.

MATERIALS AND METHODS

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Patients and tissue samples

We reviewed medical records of 470 patients, who underwent surgery for EC between January 1990 and June 2010. Approval of the Institutional Review Board of Seoul National University Hospital was obtained in advance. Of the 470, 46 were selected for diabetic group if the patient had DM at the time of diagnosis of EC. Of the 46, key paraffin-embedded tissue blocks of 11 patients were not available, and we retrieved 35 paraffin-embedded tissues from the archival files of the Department of Pathology. Each diabetic patient in diabetic group was matched to one non-diabetic patient in the non-diabetic group for age at diagnosis, preoperative body mass index, histological type, grade, and stage. Except one whose tissue blocks were not available, 34 in the non-diabetic group were included. Finally, 34 patients with paraffin-embedded tissue in each group were included in the analysis (Fig. 1).

We collected patient information regarding age at diagnosis, preoperative body mass index, presence of DM, intraoperative findings, pathologic findings, including preoperative endometrial curettage, as well as tissue specimen obtained during the surgery, FIGO stage, and follow-up results, which are summarized in Table 1. The survival time and follow-up period were calculated from the date of surgery.

As a normal control, we also investigated normal endometrial tissue blocks from 12 patients undergoing hysterectomy for leiomyoma of uterus: 8 proliferative and 4 secretory phase of the menstrual cycle.


2. Tissue microarray


Tissue microarrays (TMA) were constructed from the core biopsies (diameter 2 mm) of formalin-fixed paraffin-embedded primary EC specimens, using a trephine apparatus (Super-biochips Laboratories, Seoul, Korea). Three core biopsies were taken from each individual specimen. Normal endometrial specimens were also included in each of the array blocks.


3. Immunohistochemistry


After deparaffinization, tissues were rehydrated and subjected to antigen retrieval by immersing in pH 9.0 Tris-EDTA buffer and incubating at 100°C for 20 minutes. Endogenous peroxidase activity was blocked with 3% hydrogen peroxide for 6 minutes. After protein blocking for 30 minutes, samples were incubated with a 1:30 dilution of mouse monoclonal antibody (UJ127, Novus Biologicals, Littleton, CO, USA) at 37°C for 32 minutes. After incubating with biotinylated anti-goat IgG for 30 minutes, samples were treated with ABC reagent for another 30 minutes. After incubating for 2 minutes, using a 3,3’-diaminobenzidine substrate kit, samples were counterstained with hematoxylin. Samples were then incubated in a bluing reagent for 4 minutes. Signals were detected using an Ultra view polymer (Ventana, Tucson, AZ, USA).


4. Evaluation of the staining


Staining was evaluated simultaneously by a specialized pathologist and a gynecologic oncologist who were unaware of the patients’ clinical features. Any discrepancy was resolved by a third observer. The slides were evaluated for the distribution of staining in the tissue (cytoplasmic or stromal), the percentage of positively stained tumor cells (low, 1?10%; moderate, 11?30%; high, 31?100%), and the intensity of staining (grade 0?3). Cases were defined positive for L1CAM expression when > 5% tumor cells showed > grade 1 staining intensity. Negative cases had to show definitely no L1CAM immunoreactivity in any field.


5.  Statistical analysis


Continuous variables were compared using the student t-test, and categorical variables were compared using the chi-square test or Fisher’s exact test, as appropriate. Progression-free survival (PFS) was calculated and compared using the Kaplan-Meier method with a log rank test. A 2-sided P-value < 0.05 indicated statistical significance. The statistical analyses were performed using SPSS for Windows version 19.0 (SPSS, Chicago, IL, USA).

RESULTS

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L1 cell adhesion molecule expression

Of the 68 patients, 13 (19.1%) were positive for L1CAM immunostaining in the cytoplasm of tumor cells. L1CAM was stained with membranous pattern and was often localized in some area rather than diffusely stained (Fig. 2). Interestingly, we observed that L1CAM expression was often localized, exclusively, at the leading front of tumors irrespective of DM status. All of the 12 normal endometrial tissue samples failed to show any evidence for the expression of L1CAM in the proliferative or secretory phase. There was no difference of L1CAM expression, according to the presence of DM.


Analysis of clinicopathologic characteristics

At 50.5 months of the mean follow-up (range 2?113 months), a total of three recurrences, 2 diabetic and 1 non-diabetic patients, were observed without disease related mortality. Of the 68 cases in total, 60 (88.2%) were endometrioid histological type and 8 (11.8%) were non-endometrioid histological type: 2 serous, 2 clear cell, and 2 mucinous type in diabetic group and each one serous and clear cell type in non-diabetic group. Due to the matching process, there was no significant difference of the risk factors for recurrence between the diabetic and non-diabetic groups. Four (11.8%), two in each group did not undergo lymphadenectomy because they seemed to have little chance to have LN metastasis: grade 1 endometrioid type EC without myometrial invasion. There was no significant difference of the performance of paraaortic LN dissection between the diabetic and non-diabetic groups (35.3% vs. 20.6%, P = 0.177). Positive rate of L1CAM expression in diabetic EC patients was also similar to that in the non-diabetic EC patients (14.7% vs. 23.5%, P = 0.355) (Table 1).


L1 cell adhesion molecule expression and lymph node metastasis

Of the 64 patients, who underwent lymphadenectomy, 8 (12.5%) had LN metastasis: 4 diabetic and 4 non-diabetic EC patients. Of the 19 who underwent paraaortic lymphadenectomy, 3 (15.8%) had paraaortic LN metastasis; all of them had diabetes. Tumor recurred more in patients with positive L1CAM expression than those with negative L1CAM expression for all enrolled patients (33.3% vs. 1.6%, P = 0.019) (data not shown). However, we failed to find any significant association between L1CAM expression and LN metastasis for the entire subjects (Table 2).

Only for the diabetic EC patients (n = 34), patients with pelvic LN metastasis showed L1CAM expression more than those without LN metastasis (50.0% vs. 3.6%, P = 0.035) (Table 3). Nevertheless, there was no significant association between paraaortic LN metastasis and L1CAM expression.


L1 cell adhesion molecule expression and other risk factors for recurrence

Advanced stage (FIGO stage II, III) tumor was the only risk factor for recurrence that showed a significant association with L1CAM expression in EC (P = 0.014). Moreover, in a subgroup analysis with the diabetic EC patients, the significant relationship between advanced stage and L1CAM expression was also observed (P = 0.006). However, no significant association was found between L1CAM expression in diabetic EC patients and other known risk factors for recurrence, such as paraaortic LN metastasis, high grade tumor and deep myometrial invasion.


L1 cell adhesion molecule expression and progression-free survival

Kaplan-Meier method with log-rank test revealed that there was no significant difference of PFS between the diabetic and non-diabetic groups (data not shown). However, EC with L1CAM expression recurred significantly earlier than that without L1CAM expression (P = 0.017) (Fig. 3A). In a subgroup analysis of diabetic patients, PFS was also significantly shorter in EC patients with L1CAM expression than those without L1CAM expression (P < 0.001) (Fig. 3B).

Figures

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Fig. 1. Process for a case-control patient matching: EC, endometrial cancer; DM, diabetes mellitus.
Fig. 2. Expression of L1 cell adhesion molecule (L1CAM) in endometrial cancer (EC) tissue. Membranous immunohistochemical staining of EC tissue of L1CAM (brown) with nuclear counterstaining (blue). L1CAM-positive EC (A, endometrioid type; B, clear cell type; ×400). L1CAM-negative EC (C and D; ×400). Negative L1CAM expression in normal proliferative (E) and secretory (F) endometrial tissue (×200). Exclusive staining at the invasive tumor front at low magnification (G, H, and I; ×100). Higher magnification of the boxed areas in (G), (H), and (I) showing L1CAM expression in invading tumor cells into adjacent stroma (G-1, H-1, and I-1; ×400). (A, C, and G, EC tissue of diabetic patients; B, D, E, F, H, and I, EC tissue of non-diabetic patients).
Fig. 3. Progression-free survival according to L1 cell adhesion molecule (L1CAM) expression in endometrial cancer (EC). Kaplan-Meier survival curves for all enrolled patients (n = 68) (A) and diabetic EC patients (n = 34) (B).

Tables

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Table. 1.

Clinicopathologic characteristics.

CharacteristicsEC with DMEC without DMP
Number of patients3434
Age (years), mean (range)56.7 (31?81)56.7 (34?76)0.991
BMI (kg/m2), mean (range)28.2 (21.0?42.1)26.4 (20.5?43.4)0.086
Serum CA125 levels (U/ml), mean (range)38.8 (3.2?336.5)28.0 (4.4?307.0)0.535
FIGO stage, n (%)0.782
??IA24 (70.6)26 (76.5)
??IB3 (8.8)1 (2.9)
??II3 (8.8)3 (8.8)
??IIIC4a (11.8)4b (11.8)
Histological type, n (%)0.259
??Endometrioid28 (82.4)32 (94.1)
??Non-endometrioid6 (17.6)2 (5.9)
Histological grade, n (%)0.329
??I17 (50.0)21 (61.8)
??II, III17 (50.0)13 (38.2)
Myometrial invasion, n (%)1.000
??≤ 1/230 (88.2)30 (88.2)
??> 1/24 (11.8)4 (11.8)
LVSI, n (%)0.741
??Positive6 (18.2)5 (15.2)
??Negative27 (81.8)28 (84.8)
Primary tumor size (cm), mean (range)3.0 (0.1?13.5)2.2 (0.1?5.0)0.104
Washing cytology, n (%)0.493
??Positive for malignancy2 (5.9)0 (0)
??Negative for malignancy32 (94.1)32 (100.0)
Lymphadenectomy, n (%)1.000c
??PLND only20 (58.8)25 (73.5)0.177d
??PLND and PALND12 (35.3)7 (20.6)
??Not done2 (5.9)2 (5.9)
Number of LN harvested, mean (range)26.3 (0?50)24.5 (0?57)0.552
LN metastasis, n (%)1.000
??Positive4 (12.5)4 (12.5)
??Negative28 (87.5)28 (87.5)
Paraarortic LN metastasise, n (%)0.263
??Positive3 (25.0)0 (0)
??Negative9 (75.0)7 (100.0)
Recurrence, n (%)1.000
??Yes2 (5.9)1 (2.9)
??No32 (94.1)33 (97.1)
L1CAM expression, n (%)0.355
??Positive5 (14.7)8 (23.5)
??Negative29 (85.3)26 (76.5)

BMI, body mass index; DM, diabetes mellitus; EC, endometrial cancer; FIGO, International Federations of Gynecology and Obstetrics; LN, lymph node; LVSI, lymphovascular space invasion; PALND, paraaortic lymph node dissection; PLND, pelvic lymph node dissection..

All patients with paraaortic LN metastasis have pelvic LN metastasis.
Table. 2.

L1CAM expression and risk factors for recurrence for all enrolled patients (N = 68).

L1CAM expression
P
PositiveNegative
FIGO stage, n (%)0.014
??Early2 (3.7)52 (96.3)
??Advanced4 (28.6)10 (71.4)
Histological type0.543
??Endometrioid5 (8.3)55 (91.7)
??Non-endometrioid1 (12.5)7 (87.5)
Histological grade0.394
??I2 (5.3)36 (94.7)
??II, III4 (13.3)26 (86.7)
Myometrial invasion, n (%)0.543
??≤ 1/25 (8.3)55 (91.7)
??> 1/21 (12.5)7 (87.5)
LVSI, n (%)1.000
??Positive1 (9.1)10 (90.9)
??Negative4 (7.3)51 (92.7)
LN metastasis, n (%)0.159
??Positive2 (25.0)6 (75.0)
??Negative4 (7.1)52 (92.9)
PALN metastasis, n (%)0.530
??Positive1 (33.3)2 (66.7)
??Negative3 (18.8)13 (81.3)

FIGO, International Federations of Gynecology and Obstetrics; LN, lymph node; LVSI, lymphovascular space invasion; PALN, paraaortic lymph node..
Table. 3.

L1CAM expression and risk factors for recurrence according to the status of diabetes.

L1CAM expression of diabetic group (N = 34)
PL1CAM expression of non-diabetic group (N =34)
P
PositiveNegativePositiveNegative
FIGO stage, n (%)0.0060.511
??Early027 (100.0)2 (7.4)25 (92.6)
??Advanced3 (42.9)4 (57.1)1 (14.3)6 (85.7)
Histological type1.0000.171
??Endometrioid3 (10.7)25 (89.3)2 (6.3)30 (93.8)
??Non-endometrioid06 (100.0)1 (50.0)1 (50.0)
Histological grade1.0000.544
??I1 (5.9)16 (94.1)1 (4.8)20 (95.2)
??II, III2 (11.8)15 (88.2)2 (15.4)11 (84.6)
Myometrial invasion, n (%)0.3221.000
??≤ 1/22 (6.7)28 (93.3)3 (10.0)27 (90.0)
??> 1/21 (25.0)3 (75.0)04 (100.0)
LVSI, n (%)0.4641.000
??Positive1 (16.7)5 (83.3)05 (100.0)
??Negative2 (7.4)25 (92.6)2 (7.1)26 (92.9)
Pelvic LN metastasis, n (%)0.0351.000
??Positive2 (50.0)2 (50.0)04 (100.0)
??Negative1 (3.6)27 (96.4)3 (10.7)25 (89.3)
PALN metastasis, n (%)1.000
??Positive1 (33.3)2 (66.7)
??Negative2 (22.2)7 (77.8)

FIGO, International Federations of Gynecology and Obstetrics; LN, lymph node; LVSI, lymphovascular space invasion; PALN, paraaortic lymph node..

References

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  1. Hill EK, Dizon DS. Medical therapy of endometrial cancer: current status and promising novel treatments. Drugs 2012;72:70513.
    Pubmed CrossRef
  2. Fujimoto T, Nanjyo H, Nakamura A, Yokoyama Y, Takano T, Shoji T, et al. Para-aortic lymphadenectomy may improve disease-related survival in patients with multipositive pelvic lymph node stage IIIc endometrial cancer. Gynecol Oncol 2007;107:253-9.
    Pubmed CrossRef
  3. Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet 2009;105:103-4.
    CrossRef
  4. Weiderpass E, Persson I, Adami HO, Magnusson C, Lindgren A, Baron JA. Body size in different periods of life, diabetes mellitus, hypertension, and risk of postmenopausal endometrial cancer (Sweden). Cancer Causes Control 2000;11:185-92.
    Pubmed CrossRef
  5. Steiner E, Schmidt M, Weikel W, Koelbl H. Influence of diabetes mellitus and nodal distribution in endometrial cancer and correlation to clinico-pathological prognostic factors. Eur J Gynaecol Oncol 2006;27:477-80.
    Pubmed
  6. Raveh S, Gavert N, Ben-Ze'ev A. L1 cell adhesion molecule (L1CAM) in invasive tumors. Cancer Lett 2009;282:137-45.
    Pubmed CrossRef
  7. Brummendorf T, Kenwrick S, Rathjen FG. Neural cell recognition molecule L1: from cell biology to human hereditary brain malformations. Curr Opin Neurobiol 1998;8:87-97.
    CrossRef
  8. Fogel M, Gutwein P, Mechtersheimer S, Riedle S, Stoeck A, Smirnov A, et al. L1 expression as a predictor of progression and survival in patients with uterine and ovarian carcinomas. Lancet 2003;362:869-75.
    CrossRef
  9. Zecchini S, Bianchi M, Colombo N, Fasani R, Goisis G, Casadio C, et al. The differential role of L1 in ovarian carcinoma and normal ovarian surface epithelium. Cancer Res 2008;68:1110-8.
    Pubmed CrossRef
  10. Boo YJ, Park JM, Kim J, Chae YS, Min BW, Um JW, et al. L1 expression as a marker for poor prognosis, tumor progression, and short survival in patients with colorectal cancer. Ann Surg Oncol 2007;14:1703-11.
    Pubmed CrossRef
  11. Fogel M, Huszar M, Altevogt P, Ben-Arie A. L1 (CD171) as a novel biomarker for ovarian and endometrial carcinomas. Expert Rev Mol Diagn 2004;4:455-62.
    Pubmed CrossRef
  12. Jiang H, Guan G, Zhang R, Liu G, Cheng J, Hou X, et al. Identification of urinary soluble E-cadherin as a novel biomarker for diabetic nephropathy. Diabetes Metab Res Rev 2009;25:232-41.
    Pubmed CrossRef
  13. Gavert N, Conacci-Sorrell M, Gast D, Schneider A, Altevogt P, Brabletz T, et al. L1, a novel target of beta-catenin signaling, transforms cells and is expressed at the invasive front of colon cancers. J Cell Biol 2005;168:633-42.
    Pubmed CrossRef
  14. Sengupta U, Ukil S, Dimitrova N, Agrawal S. Expression-based network biology identifies alteration in key regulatory pathways of type 2 diabetes and associated risk/complications. PLoS One 2009;4:e8100.
    Pubmed CrossRef
  15. Hills CE, Squires PE. TGF-beta1-induced epithelial-to-mesenchy mal transition and therapeutic intervention in diabetic nephropathy. Am J Nephrol 2010;31:68-74.
    Pubmed CrossRef
  16. Holian J, Qi W, Kelly DJ, Zhang Y, Mreich E, Pollock CA, et al. Role of Kruppel-like factor 6 in transforming growth factor-beta1-induced epithelial-mesenchymal transition of proximal tubule cells. Am J Physiol Renal Physiol 2008;295:F1388-96.
    Pubmed CrossRef
  17. Hills CE, Al-Rasheed N, Al-Rasheed N, Willars GB, Brunskill NJ. C-peptide reverses TGF-beta1-induced changes in renal proximal tubular cells: implications for treatment of diabetic nephropathy. Am J Physiol Renal Physiol 2009;296:F614-21.
    Pubmed CrossRef
  18. Barri?re G, Tartary M, Rigaud M. Metformin: a rising star to fight the epithelial mesenchymal transition in oncology. Anticancer Agents Med Chem 2012;13:333-40.
    CrossRef
  19. Del Barco S, Vazquez-Martin A, Cufi S, Oliveras-Ferraros C, BoschBarrera J, Joven J, et al. Metformin: multi-faceted protection against cancer. Oncotarget 2011;2:896-917.
    Pubmed
  20. Huszar M, Pfeifer M, Schirmer U, Kiefel H, Konecny GE, Ben-Arie A, et al. Up-regulation of L1CAM is linked to loss of hormone receptors and E-cadherin in aggressive subtypes of endometrial carcinomas. J Pathol 2010;220:551-61.
    Pubmed CrossRef
  21. Gast D, Riedle S, Riedle S, Schabath H, Schlich S, Schneider A, et al. L1 augments cell migration and tumor growth but not beta3 integrin expression in ovarian carcinomas. Int J Cancer 2005;115:658-65.
    Pubmed CrossRef
  22. Geismann C, Morscheck M, Koch D, Bergmann F, Ungefroren H, Arlt A, et al. Up-regulation of L1CAM in pancreatic duct cells is transforming growth factor beta1- and slug-dependent: role in malignant transformation of pancreatic cancer. Cancer Res 2009;69:4517-26.
    Pubmed CrossRef
  23. Pfeifer M, Schirmer U, Geismann C, Sch?fer H, Sebens S, Altevogt P. L1CAM expression in endometrial carcinomas is regulated by usage of two different promoter regions. BMC Mol Biol 2010;11:64.
    Pubmed CrossRef
  24. Jawhar NM. Tissue microarray: a rapidly evolving diagnostic and research tool. Ann Saudi Med 2009;29:123-7.
    Pubmed CrossRef
  25. Shergill IS, Shergill NK, Arya M, Patel HR. Tissue microarrays: a current medical research tool. Curr Med Res Opin 2004;20:707-12.
    Pubmed CrossRef
  26. Kang S, Kang WD, Chung HH, Jeong DH, Seo SS, Lee JM, et al. Preoperative identification of a low-risk group for lymph node metastasis in endometrial cancer: a Korean gynecologic oncology group study. J Clin Oncol 2012;30:1329-34.
    Pubmed CrossRef
  27. Suh DH, Kim K, Kim JW. Major clinical research advances in gynecologic cancer in 2011. J Gynecol Oncol 2012;23:53-64.
    Pubmed CrossRef
  28. Kitajima K, Yamasaki E, Kaji Y, Murakami K, Sugimura K. Comparison of DWI and PET/CT in evaluation of lymph node metastasis in uterine cancer. World J Radiol 2012;4:207-14.
    Pubmed CrossRef
  29. Park JY, Kim EN, Kim DY, Suh DS, Kim JH, Kim YM, et al. Comparison of the validity of magnetic resonance imaging and positron emission tomography/computed tomography in the preoperative evaluation of patients with uterine corpus cancer. Gynecol Oncol 2008;108:486-92.
    Pubmed CrossRef
  30. Chung HH, Park NH, Kim JW, Song YS, Chung JK, Kang SB. Role of integrated PET-CT in pelvic lymph node staging of cervical cancer before radical hysterectomy. Gynecol Obstet Invest 2009;67:61-6.
    Pubmed CrossRef

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