Laminin C1 expression by uterine carcinoma cells is associated with tumor progression.
OBJECTIVE
Molecular markers associated with tumor progression in uterine carcinoma are poorly defined. In this study, we determine whether upregulation of LAMC1, a gene encoding extracellular matrix protein, laminin γ1, is associated with various uterine carcinoma subtypes and stages of tumor progression.


METHODS
An analysis of the immunostaining patterns of laminin γ1 in normal endometrium, atypical hyperplasia, and a total of 150 uterine carcinomas, including low-grade and high-grade endometrioid carcinomas, uterine serous and clear cell carcinoma, was performed. Clinicopathological correlation was performed to determine biological significance. The Cancer Genome Atlas (TCGA) data set was used to validate our results.


RESULTS
As compared to normal proliferative and secretory endometrium, for which laminin γ1 immunoreactivity was almost undetectable, increasing laminin C1 staining intensity was observed in epithelial cells from atypical hyperplasia to low-grade endometrioid to high-grade endometrioid carcinoma, respectively. Laminin γ1 expression was significantly associated with FIGO stage, myometrial invasion, cervical/adnexal involvement, angiolymphatic invasion and lymph node metastasis. Similarly, analysis of the endometrial carcinoma data set from TCGA revealed that LAMC1 transcript levels were higher in high-grade than those in low-grade endometrioid carcinoma. Silencing LAMC1 expression by siRNAs in a high-grade endometrioid carcinoma cell line did not affect its proliferative activity but significantly suppressed cell motility and invasion in vitro.


CONCLUSIONS
These data suggest that laminin γ1 may contribute to the development and progression of uterine carcinoma, likely through enhancing tumor cell motility and invasion. Laminin γ1 warrants further investigation regarding its role as a biomarker and therapeutic target in uterine carcinoma.
Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD, United States; Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Japan.
Hiroyasu
H
Kashima
Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
Ren-Chin
RC
Wu
Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Japan; Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, China.
Yihong
Y
Wang
Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD, United States.
Abdulrahman K
AK
Sinno
Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Japan.
Tsutomu
T
Miyamoto
Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Japan.
Tanri
T
Shiozawa
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, United States.
Tian-Li
TL
Wang
Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD, United States.
Amanda N
AN
Fader
Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD, United States; Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, United States. Electronic address: ishih@jhmi.edu.
Ie-Ming
IeM
Shih
D018262:Adenocarcinoma, Clear Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D016208:Databases, Factual; D018450:Disease Progression; D004714:Endometrial Hyperplasia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin / Q000235:genetics* / Q000378:metabolism; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism*; D015854:Up-Regulation
D007797:Laminin; D012333:RNA, Messenger; C089141:laminin gamma 1
Endometrial carcinoma; Laminin; Pathogenesis; Pathology; Uterine carcinoma