VEGF expression and microvascular density in relation to high-risk-HPV infection in cervical carcinoma – An immunohistochemical study

Available online 13 January 2012

Peer review under responsibility of Alexandria University Faculty of Medicine.

Figures & data

Figure 1 VEGF immunostaining. (A) Grade II adenocarcinoma showing strong cytoplasmic VEGF immunostaining in both neoplastic epithelial (thin arrow) and stromal cells (thick arrow). (B) Grade II adenocarcinoma showing moderate cytoplasmic VEGF immunostaining ((A and B) anti-VEGF, 200×). (C) Grade III squamous cell carcinoma showing moderate cytoplasmic VEGF immunostaining in epithelial cells. (D) Grade III squamous cell carcinoma showing heterogeneous cytoplasmic VEGF immunostaining with weak staining in areas (arrow head) and strong intensity in others ((C and D) anti-VEGF, 400×).

Table 1 Relation between VEGF intensity and histologic subtypes of cervical carcinoma.

	VEGF intensity scores			Total	P
	1	2	3
Histologic subtypes
Squamous cell carcinoma
No.	3	5	9	17	0.315
%	42.9	83.3	52.9	56.7
Adenocarcinoma
No.	4	1	6	11
%	57.1	16.7	35.3	36.7
Adenosquamous carcinoma
No.	0	0	2	2
%	0	0	11.8	6.7

P: statistically significant at <0.05.

Table 2 Relation between VEGF staining density and histologic subtypes of cervical carcinoma.

	VEGF density scores		Total	P
	1	2
Histologic subtypes
Squamous cell carcinoma
No.	14	3	17
%	82.4	23.1	56.7
Adenocarcinoma
No.	2	9	11	0.002^*
%	11.8	69.2	36.7
Adenosquamous carcinoma
No.	1	1	2
%	5.9	7.7	6.7

* P: statistically significant at <0.05.

Table 3 Relation between VEGF staining intensity and cervical carcinoma grade.

	Cervical carcinoma grades		Total
	Low grade	High grade
VEGF intensity scores
1
No.	7	0	7
%	63.6	0	23.3
2
No.	2	4	6
%	18.2	21.1	20.0
3
No.	2	15	17
%	18.2	78.9	56.7
Total
No.	11	19	30
%	100.0	100.0	100.0
χ^2	16.66
P value	<0.0001^*

* P: statistically significant at <0.05.

Table 4 Relation between VEGF staining density and cervical carcinoma grade.

	Cervical carcinoma grades		Total
	Low grade	High grade
VEGF density scores
1
No.	1	16	17
%	9.1	84.2	56.7
2
No.	10	3	13
%	90.9	15.8	43.3
Total
No.	11	19	30
%	100.0	100.0	100.0
P of Fisher exact test	<0.0001^*

* P: statistically significant at <0.05.

Figure 2 Assessment of MVD using CD34 antibody and HPV antigen immune expression. (A) Grade IV squamous cell carcinoma, (B) grade II adenocarcinoma, (C) adenosquamous carcinoma, (A–C) showing CD34 positive-tumor blood vessels, (D) grade I adenocarcinoma showing positive CD34 staining of individual endothelial cells forming no visible lumen (arrow). ((A–D) anti-CD34, 200×). (E) Grade II squamous cell carcinoma showing strong positive nuclear HPV immunostaining (arrow). (F) Grade II adenocarcinoma showing strong positive nuclear HPV immunostaining (arrow). ((E and F) anti-HPV, 400×).

Table 5 Relation between HPV expression and cervical carcinoma grade.

	Cervical carcinoma grade		Total
	Low grade	High grade
HPV expression
Positive
No.	9	19	28
%	81.8	100	93.3
Negative
No.	2	0	2
%	18.2	0	6.7
Total
No.	11	19	30
%	100.0	100.0	100.0
P of Fisher exact test	0.13

P: statistically significant at <0.05.

Table 6 Relation between VEGF intensity and MVD.

VEGF intensity	N	Mean	S.D.	Min.	Max.	ANO-VA	P value
Score 1	7	28.1200	8.03770	17.90	39.40	12.301	0.0001^*
Score 2	6	45.9167	15.26832	26.40	70.20
Score 3	17	61.1082	16.82993	34.50	90.20
Total	30	50.3727	20.02574	17.90	90.20

* P: statistically significant at <0.05.

Table 7 Relation between VEGF density and MVD.

VEGF density	Mean	S.D.	Min.	Max.	t	P
⩽50%	57.2782	16.97857	26.40	90.20	5.368	0.028^*
>50%	41.3423	20.70976	17.90	77.20
Total	50.3727	20.02574	17.90	90.20

* P: statistically significant at <0.05.

Table 8 Relation between HPV expression and VEGF intensity.

	VEGF intensity score			Total
	1	2	3
HPV
Positive
No.	5	6	17	28
%	71.4	100.0	100.0	93.3
Negative
No.	2	0	0	2
%	28.6	0	0	6.7
Total
No.	7	6	17	30
%	100.0	100.0	100.0	100.0
P	0.042^*

* P: statistically significant at <0.05.

Table 9 Relation between HPV expression and VEGF density.

	VEGF density score		Total
	1	2
HPV
Positive
No.	17	11	28
%	100.0	84.6	93.3
Negative
No.	0	2	2
%	0	15.4	6.7
Total
No.	17	13	30
%	100.0	100.0	100.0
P of Fisher exact test	0.179

P: statistically significant at <0.05.

Table 10 Logistic regression analysis.

	Wald χ^2	P value	Odds ratio	95.0% C.I.
				Lower	Upper
MVD	3.560	0.053^*	1.570	0.983	2.508
HPV	0.01	0.98	231.34	0.03	456.11
VEGF intensity	0.60	0.44	2.58	0.24	28.03
VEGF density	0	0.99	1.74	0.99	3.123

* P: statistically significant at <0.05.

Figure 3 ROC curve for accuracy of MVD to predict grade of cervical carcinoma.