Table 2.

Relationship between Tumor NRAS+ and BRAF+ Mutational Status and Cliniopathologic Features for First Primary Melanomas from 892 Patients^a

				Adjusted for Study Centerb				Fully Adjustedc
	No. (%)			Compared with Wildtype Melanomas				Compared with Wildtype Melanomas
	Wildtype	NRAS+	BRAF+	Adjusted NRAS+		Adjusted BRAF+		Adjusted NRAS+		Adjusted BRAF+
Characteristic	(n = 503)	(n = 122)	(n = 267)	OR (95% CI)	Pd	OR (95% CI)	Pd	OR (95% CI)	Pd	OR (95% CI)	Pd
Sex
Male	279 (55)	70 (57)	144 (54)	Reference	.83	Reference	.54	Reference	.59	Reference	.33
Female	224 (45)	52 (43)	123 (46)	1.0 (0.6–1.4)		1.1 (0.8–1.5)		1.1 (0.7–1.8)		1.2 (0.8–1.7)
Age at diagnosis, years
<50	149 (30)	25 (21)	125 (47)	Reference	.07d	Reference	<.001d	Reference	.11d	Reference	.001d
50–69	201 (40)	54 (44)	100 (37)	1.6 (1.0–2.7)		0.6 (0.4–0.9)		1.5 (0.9–2.6)		0.7 (0.5–1.0)
>70	153 (30)	43 (35)	44 (16)	1.7 (1.0–3.0)		0.4 (0.2–0.5)		1.7 (0.9–3.1)		0.5 (0.3–0.8)
Anatomic site
Trunk/pelvis	198 (39)	54 (44)	147 (55)	Reference	.007	Reference	<.001	Reference	.011	Reference	.13
Scalp/neck	40 (8)	1 (1)	11 (4)	0.1 (0.01–0.7)		0.4 (0.2–0.7)		0.1 (0.01–0.6)		0.6 (0.3–1.3)
Face/ears/othere	69 (14)	10 (8)	18 (7)	0.5 (0.3–1.1)		0.4 (0.2–0.6)		0.6 (0.3–1.3)		0.7 (0.4–1.3)
Upper extremities	95 (19)	37 (30)	43 (16)	1.4 (0.9–2.3)		0.6 (0.4–1.0)		1.4 (0.8–2.3)		0.6 (0.4–1.0)
Lower extremities	101 (20)	20 (16)	48 (18)	0.7 (0.4–1.3)		0.7 (0.4–1.0)		0.6 (0.3–1.2)		0.6 (0.4–0.9)
Histologic subtype
Superficial spreading	320 (64)	80 (66)	227 (85)	Reference	.002	Reference	<.001	Reference	.17	Reference	<.001
Nodular	38 (8)	21 (17)	17 (6)	2.2 (1.2–4.0)		0.7 (0.4–1.2)		1.1 (0.6–2.3)		0.5 (0.2–1.0)
Lentigo maligna	90 (18)	9 (7)	15 (6)	0.4 (0.2–0.8)		0.2 (0.1–0.4)		0.5 (0.2–1.1)		0.4 (0.2–0.7)
Unclassified/otherf	55 (11)	12 (10)	8 (3)	0.9 (0.5–1.8)		0.2 (0.1–0.5)		0.6 (0.3–1.3)		0.2 (0.1–0.5)
Breslow thickness, mm
0.01–1.00	349 (69)	59 (48)	164 (61)	Reference	<.001	Reference	.01	Reference	.87	Reference	.34
1.01–2.00	86 (17)	34 (28)	74 (28)	2.3 (1.4–3.8)		1.8 (1.2–2.6)		1.3 (0.7–2.3)		1.4 (0.9–2.3)
2.01–4.00	49 (10)	19 (16)	21 (8)	2.2 (1.2–4.1)		0.9 (0.5–1.5)		1.1 (0.5–2.4)		0.9 (0.4–1.9)
>4.00	19 (4)	10 (8)	8 (3)	3.2 (1.4–7.3)		0.9 (0.4–2.1)		1.3 (0.4–3.7)		0.9 (0.3–2.7)
Ulceration
Absent	467 (93)	104 (85)	248 (93)	Reference	.013	Reference	.84	Reference	.85	Reference	.54
Present	36 (7)	18 (15)	19 (7)	2.2 (1.2–4.0)		0.9 (0.5–1.7)		1.1 (0.5–2.4)		1.3 (0.6–2.6)
Mitoses
Absent	319 (63)	43 (35)	129 (48)	Reference	<.001	Reference	<.001	Reference	.04	Reference	.02
Present	184 (37)	79 (65)	138 (52)	3.1 (2.1–4.8)		1.8 (1.3–2.4)		1.8 (1.0–3.3)		1.7 (1.1–2.6)
Growth phase
Radial	196 (39)	22 (18)	68 (25)	Reference	<.001	Reference	.002	Reference	.11	Reference	.12
Vertical	307 (61)	100 (82)	199 (75)	3.2 (1.9–5.3)		1.7 (1.2–2.4)		1.7 (0.9–3.2)		1.4 (0.9–2.2)
TIL grade
Absent	96 (19)	38 (31)	45 (17)	Reference	<.001d	Reference	.39d	Reference	.002d	Reference	.74d
Nonbrisk	334 (66)	75 (61)	186 (70)	0.6 (0.4–0.9)		1.3 (0.8–1.9)		0.5 (0.3–0.8)		1.0 (0.7–1.6)
Brisk	73 (15)	9 (7)	36 (13)	0.3 (0.1–0.6)		1.2 (0.7–2.2)		0.3 (0.1–0.7)		1.1 (0.6–2.0)

Abbreviations: OR, odds ratio; TIL, tumor infiltrating lymphocyte.

^aWe used polytomous logistic regression to estimate the odds ratios and 95% confidence intervals with NRAS+ and BRAF+ melanoma simultaneously compared to wildtype. Melanomas (n = 20) with one or more data points missing for ulceration (n = 19), mitoses (n = 19), growth phase (n = 19), or TIL grade (n = 20) were excluded.

^bAdjusted for study center.

^cIncluded all variables in the table and adjusted for study center.

^dWhere noted for, linear trend was tested using the Wald statistic with the variable treated as a single ordinal variable.

^eOther includes melanomas on the face/ears and other head/neck melanomas with unspecified sites.

^fOther includes acral lentiginous, spindle cell, nevoid, and Spitzoid melanomas.