Non-classical HLA-class I expression in serous ovarian carcinoma: Correlation with the HLA-genotype, tumor infiltrating immune cells and prognosis

Figures & data

Table 1. Patients' characteristics

	Cohort		HLA-A2			HLA-otherwise
	n	%	n	% of the cohort	% of the subgroup	n	% of the cohort	% of the subgroup
Patients eligible for analysis	72	100	42	58	57	30	42	43
Age median	61	36–86^**	61		35–84^**	60		36–86^**
Age less than 60	38	53	20	53	47	18	47	60
Surgical staging
III a, b, c	54	51	27	50	64	27	50	90
IV	18	15	15	83	35^***	3	17	10^***
Differentiation grade
Low	2	3	1	50	2	1	50	3
2	17	24	10	59	23	7	41	24
3	52	73	31	60	72	22	42	72
High	69	97	41	59	95	29	42	96
Treatments
Primary surgery	56	78	33	59	78	23	41	76
Radical surgery	9	12	3	33	7^***	6	67	20
Secondary surgery	14	19	8	57	19	6	43	20
Platinum-based chemotherapy	69	96	41	59	97	28	41	93
Number of chemotherapy cycles
6 and less	27	37	13	48	31	14	52	46
More than 6	45	62	29	64	69	16	36	53
Radiotherapy	3	4	3	100	7^***	0	0	0

** =range.

*** p > 0.001.

Table 2. Cumulative survival according to patients' HLA-A genotype and HLA-G and E tumor cells expresssion

		Cohort			HLA_A02			HLA_A otherwise
HLA-G and E tumor expression		N	%	Cumulative survival at 5 years	N	% of the cohort	Cumulative survival (5 years)	N	% of the cohort	Cumulative survival (5 years)
All		72	100	22	42	58	14	30	42	33
HLA-G	Positive	14	20	4	7	50	0^#	7	50	28
	Negative	58	80	22	35	60	2	23	40	31
HLA-E	Pathologic	50	70	14	31	62	3	19	38	32
	Normal	22	30	40	11	50	36	11	50	36

# All patients are dead after 2 y.

Figure 1. (A–F) Probability of survival correlated to expression of HLA-G and HLA-E, presented by Kaplan–Meier. Pathologic (X) or normal expression (•) in serous adenocarcinoma tumor cells. (A) HLA-G in the total cohort N.S. (B) HLA-G in worst prognosis group (HLA-A*02) p = 0.0003. (C) HLA-G in otherwise group (HLA-OW) N.S. (D) HLA-E in the total cohort p = 0.003. (E) HLA-E in worst prognosis group (HLA-A*02) p = 0.0003. (F) HLA-E in better prognosis group (HLA-OW) N.S.

Figure 2. Tumor cells expressing HLA-G shows aberrant HLA-E expression and loss of classical MHC expression (A) HLA-G. (B) HLA-E, score 3. (C) Classical MHC class I HC.

Figure 3. Cumulative survival by Kaplan–Meier analysis. All cases are HLA-G positive tumors with concordant loss of classical MHC. The worst prognosis was only significantly determined by HLA-A*02 genotype. HLA-A*02 (X), HLA-A otherwise (•). p = 0.003.

Table 3. Characteristic of malignant cells obtained from ascites

	Histology	HLA-A*02	HLA-G		HLA-E
Patients	Kolumn1	Genotype	Primary tumor	Metastatic tissue	Primary tumor	Metastatic tissue
1–68	Serous adenocarcinoma	yes	neg	pos	pathologic	pathologic
2–71	Serous adenocarcinoma	yes	neg	pos	pathologic	pathologic
4–76	Serous adenocarcinoma	no	neg	pos	pathologic	pathologic
5–79	Serous adenocarcinoma	no	neg	pos	pathologic	pathologic
7–82	Serous adenocarcinoma	no	neg	pos	pathologic	pathologic
6–80	Serous adenocarcinoma	no	NA	pos	NA	pathologic
9–84	Serous adenocarcinoma	no	NA	pos	NA	pathologic
10–86	Serous adenocarcinoma	no	neg	neg	normal	normal

Table 4. Immunocomptentent infiltrating cells

				Tumor infiltrating CD8^+ ^#						Tumor infiltrating Fox3p^+^#
Tumor phenotype				Cohort		Worst N=42		Otherwise N=30		Cohort		Worst		Otherwise
		N	%	N	% of the all cohort	N	% of the all cohort	N	% of the all cohort	N	% of the all cohort	N	% of the all cohort	N	% of the all cohort
cohort		72	100	36	50	19	26	17	24	22	31	11	15	11	15
HLA-G	Positive	14	20	5	36	1	7	4	29	4	29	0	0	4	29
	Pegative	58	80	36	62	18	31	13	22	18	31	11	19	7	12
HLA-E	Pathologic	50	70	25	50	14	28	11	22	17	34	9	18	8	16
	Normal	22	30	11	50	5	23	6	27	5	23	2	9	3	14

^# presence of more than score 1 is considered positive.

Figure 4. Cumulative survival by Kaplan–Meier analysis. HLA-A*02 patients with HLA-G positive tumor cells and lack of CD8⁺ lymphocytes (X), compared to HLA-A otherwise, HLA-G negative tumor cells and presence of CD8⁺ lymphocytes (•);. p = 006.