Epidermal Growth Factor Receptor as Predicting Factor on Biochemical Recurrence after Radical Prostatectomy: A Prospective Study

Jeong Woo Lee; Kang Su Cho; Kyung Seok Han; Eun Kyoung Kim; Jae Young Joung; Ho Kyung Seo; Jinsoo Chung; Weon Seo Park; Kang Hyun Lee

doi:10.4111/kju.2008.49.11.974

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Lee, Cho, Han, Kim, Joung, Seo, Chung, Park, and Lee: Epidermal Growth Factor Receptor as Predicting Factor on Biochemical Recurrence after Radical Prostatectomy: A Prospective Study

Original Article

Korean J Urol 2008;49(11):974-980.

Published online: 20 January 2008

DOI: https://doi.org/10.4111/kju.2008.49.11.974

Epidermal Growth Factor Receptor as Predicting Factor on Biochemical Recurrence after Radical Prostatectomy: A Prospective Study

Jeong Woo Lee¹, Kang Su Cho, Kyung Seok Han, Eun Kyoung Kim, Jae Young Joung, Ho Kyung Seo, Jinsoo Chung, Weon Seo Park², Kang Hyun Lee

From the Urologic Oncology Clinic, National Cancer Center, Goyang, Korea

¹Department of Urology, Seoul National University Hospital, Seoul, Korea

²Department of Pathology, National Cancer Center, Goyang, Korea

Received 13 June 2008 Revised 25 September 2008

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

We investigated epidermal growth factor receptor (EGFR) expression in prostate cancer (PCa) and their potential role as predicting factor on biochemical recurrence (BCR).

Materials and Methods

Between February 2005 and February 2007, EGFR expression were prospectively evaluated in a consecutive series of 88 PCa patients with the following characteristics: 66 patients treated with retropubic radical prostatectomy (RRP); 22 patients treated with neoadjuvant hormonal therapy followed by RRP. The relationship between EGFR expression and several clinicopathologic parameters were evaluated. The probability of BCR-free survival was determined using the Kaplan-Meier method.

Results

EGFR expression, was evaluated by immunohistochemistry, was found in 31 of 88 (35.2%) patients. 8 of 31 EGFR-positive patients (25.8%) had BCR, whereas only 5 of 57 EGFR-negative patients (8.8%) had BCR (p=0.031) during a median follow-up of 21 months. Among several variables, high serum prostate-specific antigen values (≥20), extraprostatic extension, seminal vesicle invasion, and EGFR expression were the significant predictors of BCR on univariate analysis. But, multivariate analysis showed that no variable was significant predictor of BCR. EGFR-negative patients had a significantly longer mean BCR-free survival time than EGFR-positive patients (p=0.027).

Conclusions

EGFR expression could be an potential predicting factor on BCR following RRP.

Keywords: Epidermal growth factor receptor, Prostate cancer, Biochemical recurrence

References

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Fig. 1.

H&E and immunohistochemical evaluation of epidermal growth factor receptor (EGFR) expression in prostate cancer. (A) EGFR-positive tumor (blackish stained) (x200), (B) EGFR-negative tumor (x200).

Fig. 2.

Kaplan-Meier method estimates of likelihood of remaining free of biochemical recurrence as related to epidermal growth factor receptor expression (log rank, p=0.027). BCR: biochemical recurrence, EGFR: epidermal growth factor receptor.

Table 1.

Patient characteristics

Classification	No. of patients (%)
PSA (ng/ml)
≤4.0	6 (6.8)
4.1–10.0	34 (38.6)
10.1–20.0	19 (21.6)
≥20.1	29 (33.0)
Gleason score
2–6	33 (37.5)
7–10	55 (62.5)
Clinical stage
cT1	14 (15.9)
cT2	55 (62.5)
cT3	19 (21.6)
cT4	0 (0)
Pathologic stage
pT2	56 (63.7)
pT3	31 (35.2)
pT4	1 (1.1)
Surgical margin status
Positive	17 (19.3)
Negative	71 (80.7)
Treatment option
RRP only	66 (75.0)
NHT＋RRP	22 (25.0)

PSA: prostate-specific antigen, RRP: radical retropubic prostatec tomy, NHT: neoadjuvant hormonal therapy

Table 2.

Correlation between immunohistochemistry staining for EGFR and clinicopathologic factors

Classification	RRP only group			RRP＋NHT group			Total
	No. of patients (%)		No. of patients (%)				No. of patients (%)
	EGFR＋	EGFR−	p-value	EGFR＋	EGFR−	p-value	EGFR＋	EGFR−	p-value
	(n=22)	(n=44)		(n=9)	(n=13)		(n=31)	(n=57)
PSA (ng/ml)			0.038			0.318			0.023
≤4.0 (n=6)	0 (0.0)	6 (100)		0 (0.0)	0 (0.0)		0 (0.0)	6 (100)
4.1–10.0 (n=34)	9 (26.5)	23 (73.5)		0 (0.0)	2 (100)		9 (26.5)	25 (73.5)
10.1–20.0 (n=19)	8 (47.1)	9 (52.9)		1 (50.0)	1 (50.0)		9 (47.4)	10 (52.6)
≥20.1 (n=29)	5 (45.5)	6 (54.5)		8 (44.4)	10 (55.6)		13 (44.8)	16 (55.2)
Gleason score			0.381			0.616∗			0.257
2–6 (n=33)	8 (27.6)	21 (72.4)		1 (25.0)	3 (75.5)		9 (27.8)	24 (72.2)
7–10 (n=55)	14 (37.8)	23 (62.2)		8 (44.4)	10 (55.6)		22 (40.0)	33 (60.0)
Clinical stage			0.842			0.674∗			0.850
cT1 (n=14)	4 (28.6)	10 (71.4)		0 (0.0)	0 (0.0)		4 (28.6)	10 (71.4)
cT2 (n=55)	14 (33.3)	28 (66.7)		6 (46.2)	7 (53.8)		20 (36.4)	35 (63.6)
cT3 (n=19)	4 (40.0)	6 (60.0)		3 (33.3)	6 (66.7)		7 (26.8)	12 (63.2)
Pathologic stage			0.124			0.690			0.136
pT2 (n=56)	13 (27.7)	34 (72.3)		4 (44.4)	5 (55.6)		17 (30.4)	39 (69.6)
pT3 (n=31)	9 (47.4)	10 (52.6)		5 (41.7)	7 (58.3)		14 (45.2)	17 (54.8)
pT4 (n=1)	0 (0.0)	0 (0.0)		0 (0.0)	1 (100)		0 (0.0)	1 (100)
Seminal vesicle invasion			0.034∗			0.655∗			0.062∗
Positive (n=9)	3 (100)	0 (0.0)		3 (50.0)	3 (50.0)		6 (66.7)	3 (33.3)
Negative (n=79)	19 (30.2)	44 (69.8)		6 (37.5)	10 (62.5)		25 (31.6)	54 (68.4)
Perineural invasion			0.381			1.000∗			0.349
Positive (n=48)	14 (37.8)	23 (62.2)		5 (45.5)	6 (54.5)		19 (39.6)	29 (60.4)
Negative (n=40)	8 (27.6)	21 (72.4)		4 (36.4)	7 (63.6)		12 (30.0)	28 (70.0)
Lymphovascular invasion			0.467∗			1.000∗			0.508
Positive (n=11)	4 (44.4)	5 (55.6)		1 (50.0)	1 (50.0)		5 (45.5)	6 (54.5)
Negative (n=77)	18 (31.6)	39 (68.4)		8 (40.0)	12 (60.0)		26 (33.8)	51 (66.2)
Surgical margin status			0.136			0.544∗			0.089
Positive (n=17)	7 (50.0)	7 (50.0)		2 (66.7)	1 (33.3)		9 (52.9)	8 (47.1)
Negative (n=71)	15 (28.8)	37 (71.2)		7 (36.8)	12 (63.2)		22 (33.3)	44 (66.7)
Neoadjuvant hormonal therapy									0.519
Received (n=22)							9 (40.9)	13 (59.1)
None (n=66)							22 (33.3)	44 (66.7)

EGFR: epidermal growth factor receptor, PSA: prostate-specific antigen, RRP: radical retropubic prostatectomy. ∗: Fisher's exact test

Table 3.

Univariate and multivariate analysis of prognostic factors for biochemical recurrence

Variable	HR	95% CI	p-value
Univariate
PSA≥20	3.606	1.176–11.059	0.025
Gleason score≥7	4.001	0.885–18.086	0.072
Extraprostatic extension	6.703	1.841–24.401	0.004
Seminal vesicle invasion	7.472	2.416–23.102	＜0.001
EGFR (＋)	3.286	1.073–10.062	0.037
Surgical margin (＋)	1.819	0.558–5.931	0.321
Multivariate
PSA≥20	1.417	0.375–5.354	0.607
Extraprostatic disease	4.313	0.973–19.118	0.054
Seminal vesicle invasion	1.956	0.484–7.904	0.102
EGFR (＋)	2.302	0.677–7.827	0.123

PSA: prostate-specific antigen, EGFR: epidermal growth factor receptor, HR: hazard ratio, CI: confidence interval

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