. 2015 Feb 7;466(4):363–373. doi: 10.1007/s00428-015-1719-6

Table 2.

Characteristics of included studies

	First author	Year	Country	Sample size	Tumor site	TNM stage	Reference standard	Nodal metastasis ^a	Genes	Method	Tissue	Cutoff
Gene amplification	Hanken	2014	Germany	255	Oral cavity	All	pN	46 %	CCND1	FISH	FFPE	G/C ratio >2.0
	Yoshioka	2013	Japan	25	Oral cavity	All	pN	60 %	11q13.3	CGH	FFPE	G/C ratio >1.12
	Sugahara	2011	Japan	54	Oral cavity	All	pN	41 %	11 genes in 11q13^c	CGH	Fresh frozen	G/C ratio >1.5 in ≥3 genes
	Pathare	2011	India	97	Oral cavity	N.A.	pN	56 %	11q13	CGH	Fresh frozen	G/C ratio >1.25
	Michikawa	2011	Japan	127	Oral cavity	All	pN	42 %	CCND1	FISH	Fixed FNA	G/C ratio >1.2 and gene/cell ratio >3
	Mahdey	2011	Malaysia	50	Cheek and tongue	All	pN	54 %	CCND1	FISH	FFPE	G/C Ratio >2.0
	Prapinjumrune^b	2010	Japan	60	Tongue	T1-2	pN or FU	43 %	FADD	RT-PCR	FFPE	G/C ratio >1.5
	Myo	2005	Japan	45	Oral cavity	cT1-2N0	pN or FU	38 %	CCND1	FISH	Fixed FNA	>20 % of 100 cells ≥3 spots
	Fujii	2001	Japan	23	Tongue	All	pN or FU	61 %	CCND1	FISH	FFPE	>20 % of 100 cells ≥3 spots
Protein overexpression	Huang	2012	Taiwan	264	Oral cavity	All	pN	48 %	CCND1	IHC	FFPE	10 % staining
	Prapinjumrune ^b	2010	Japan	60	Tongue	T1-2	pN or FU	40 %	FADD	IHC	FFPE	29.2 % staining
	Shah	2009	India	135	Cheek and tongue	All	pN	33 %	CCND1	IHC	FFPE	10 % staining
	Maahs	2007	Brazil	45	Oral cavity	All	pN	51 %	CCND1	IHC	FFPE	1 % staining
	Rodolico	2005	Italy	97	Lower lip	Any T cN0	pN	13 %	CCND1	IHC	FFPE	1 % staining
	Miyamoto ^b	2003	Japan	41	Oral cavity	All	pN	20 %	CCND1	IHC	FFPE	10 % staining
	Takes	2002	Netherlands	52	Oral cavity	All	pN	63 %	CCND1	IHC	FFPE	5 % staining
	Goto	2002	Japan	41	Tongue	cT1-2	pN	44 %	CCND1	IHC	FFPE	33 % staining
	Kuo	1999	Taiwan	88	Oral cavity	All	pN	60 %	CCND1	IHC	FFPE	10 % staining
	Bova	1999	Australia	147	Tongue	All	pN	23 %	CCND1	IHC	FFPE	10 % staining

TNM tumor-node-metastasis, FISH fluorescence in situ hybridization, CGH comparative genomic hybridization, IHC immunohistochemistry, FFPE formalin-fixed paraffin-embedded, FNA fine needle aspiration, G/C gene/chromosome

^aHistologically proven nodal metastasis

^bThese studies correlated both gene amplification and protein overexpression with nodal metastasis

^cTPCN2, MYEOV, CCND1, ORAOV1, FGF4, TMEM16A, FADD, PPFIA1, CTTN, SHANK2, DHCR7