Table 1.

Studies examining the role of SDF-1alpha/CXCR4 in endometrial cancer (N = 4)

Author	Sample population	Study design and lab methods	Important covariates	Primary results with estimates	Secondary findings
Mizokami (2004)	Human samples Human endometrial cancers (N = 41) obtained following hysterectomy—source of sample not described Cell lines Five endometrial cancer cell lines: AMEC, Ishikawa, HEC1A, HEC50, RL95—purchased from commercial source	Cross-sectional: association between protein expression (SDF-1alpha and CXCR4) and histologic grade Lab methods 1.) RT-PCRa 2.) IHCb 3.) Western blot	Exposure Mean protein expression of SDF-1alpha and CXCR4 in endometrial cancer tissues Outcome Histologic grade (grade 1 and 2 tumors vs. grade 3 tumors)	Mean CXCR4 expression was greater in Grade 1/2 tumors vs. Grade 3 tumors (p < 0.05) -nonparametric Mann-Whitney U-test Mean SDF-1alpha expression was greater in Grade 1/2 tumors vs. Grade 3 tumors (p < 0.05) -nonparametric Mann-Whitney U-test	CXCR4 mRNA and protein was detected in cell lines, the normal endometrium of the secretory phase, and endometrial cancer tissue (RT-PCR & Western blot) Stromal expressions of SDF-1alpha and CXCR4 were not significantly different among tumors of different grade (IHC)
Kodama (2007)	Human samples Human endometrial cancers (N = 166) obtained following hysterectomy and oophorectomy at the Okayama Hospital (Japan) between Jan, 1997 and Nov, 2004 -patients with distant metastases excluded	Cross-sectional: association between CXCR4 protein expression and clinicopathological features (listed in important covariates) Longitudinal: association between CXCR4 expression and disease free survival Lab methods 1.) IHC 2.) RT-PCR	Exposure Dichotomous CXCR4 protein expression (positive vs. negative) in endometrial cancer tissues Outcomes FIGO stage (late/early), myometrial invasion (pos/neg), cervical involvement (pos/neg), lymphovascular invasion (pos/neg), lymph node metastasis (pos/neg), ovarian metastasis (pos/neg) Disease free survival and overall survival	Positive CXCR4 was significantly associated with positive myometrial invasion, late FIGO stage, positive lymphovascular invasion, and positive ovarian metastasis (p < 0.05) -chi-square test Disease free survival rates were not significantly different in patients with positive CXCR4 expression compared to negative expression (p = 0.089) -log rank test statistic Overall survival rates were significantly different in patients with positive CXCR4 expression compared to negative expression (p = 0.035) -log rank test statistic	CXCR4 expression was not an independent prognostic factor for endometrial cancer patient survival -Cox proportional hazards model CXCR4 mRNA levels (RT-PCR) were observed to be significantly higher in tumors with positive CXCR4 protein (IHC) expression (p < 0.0001)
Tsukamoto (2007)	Human samples Human endometrial adenocarcinomas (N = 34) obtained from patients at Nagoya University Hospital between 1994 and 2002 Cell lines Five endometrial cancer cell lines: AMEC, Ishikawa, HEC1A, HEC50, RL95—purchased from commercial source	Cross-sectional: association between CXCR4 protein expression and myometrial invasion Lab methods 1.) IHC 2.) Western blot 3.) ELISAd 4.) Migration assay	Exposure Mean CXCR4 protein expression in endometrial cancer tissues Outcomes Myometrial invasion (more than 1/2 invaded vs. less than 1/2 invaded)	Mean CXCR4 expression was significantly greater in tumors that invaded more than half of the myometrium compared to tumors that invaded less than one half of the myometrium (p < 0.05) -nonparametric Mann-Whitney U-test	CXCR4 protein was expressed in endometrial cancer cell lines (Western blot) Endometrial cancer cells co-cultured with uterine smooth muscle cells increased migration of cells compared to cells cultured alone (MAc) Normal human uterine smooth muscle cells produce SDF-1alpha (ELISA) SDF-1alpha activated the PI-3 K/Akt pathway (Western blot) Migration was inhibited by CXCR4 antibodies and antagonists (MA)
Gelmini (2009)	Human samples Endometrial cancer patients (N = 41) consecutively admitted for surgery at the Department of Gynecology (University of Florence) from November, 2006 to January, 2008 Experimental component in vivo mouse model	Cross-sectional: association between mRNA and protein expression (CXCR4 and SDF-1alpha) and histologic grade Lab methods 1.) RT-PCR 2.) IHC 3.) in vivo model	Exposures Median CXCR4 mRNA expression Median SDF-1alpha mRNA expression Outcomes Histologic grade (early grade vs. late grade)	Median CXCR4 mRNA expression was significantly lower in grade 1 tumors compared to grade 2/3 tumors (p = 0.035) -statistical method not described—assumption: Mann-Whitney U-test or Student’s t-test Median SDF-1alpha mRNA expression was not significantly different between grade 1 tumors and grade 2/3 tumors -statistical method not described	SDF-1alpha mRNA expression was significantly higher in normal tissues compared to cancers (RT-PCR) CXCR4 mRNA was significantly higher in cancers than in normal counterparts (RT-PCR) All endometrial cancers had a high, uniform expression of CXCR4 protein regardless of grade (IHC) After injection of cancer cells, metastases were evident. Treatment with a CXCR4 neutralizing monocolonal antibody reduced the number and size of all metastases (in vivo model)

^aRT-PCR: Reverse transcription polymerase chain reaction ^bIHC: Immunohistochemistry ^cMA: Migration assay ^dELISA: enzyme-linked immunosorbent assay