Elsevier

Theriogenology

Volume 93, 15 April 2017, Pages 33-39
Theriogenology

The association between the serum concentration of canine prostate specific esterase (CPSE) and the size of the canine prostate

https://doi.org/10.1016/j.theriogenology.2017.01.032Get rights and content

Highlights

  • The serum concentration of CPSE was associated with the relative size and the contour of the prostate (P < 0.001).

  • Dogs with clinical signs of prostatic hyperplasia had a prostate that was enlarged 2.5 times the gland of a young dog.

  • A CPSE concentration estimating a 2.5 times prostate size increase in dogs ≥4 years, was 90 ng/mL, SE 85% and SP 72%.

  • Ninety-five per cent of the dogs, all ≥4 years, had a prostate larger than considered normal for dogs 1–4 years old.

Abstract

Benign prostatic hyperplasia (BPH) is an age-related disorder in the intact male dog that is associated with an increase in the prostatic size. Ultrasonography gives a reliable estimate of the prostatic size, but a method for screening the prostate size using a serum sample has advantages, such as requiring less expensive equipment. The primary aim of the study was to study the association between the concentration of the circulating biomarker canine prostate specific esterase (CPSE) and prostatic size. Seventy-nine dogs that were four years old or older were included in the study. Ultrasonography was used for calculating the volume of the prostate. The calculated volume was divided by an estimate of the normal prostatic volume in dogs aged one to four years, to determine the relative prostatic size: the size of the prostate in relation to the normal size in dogs 1–4 years old (Srel). CPSE was analyzed from serum samples. Multiple linear regression analysis was used for studying associations between variables. Prediction intervals for the relative prostatic size based on CPSE concentrations were calculated, as were receiver operating curves for CPSE concentrations predicting Srel. The concentration of CPSE was associated with the relative size and contour of the prostate (P < 0.001). All dogs with clinical signs of BPH had an Srel ≥ 2.5. A CPSE concentration of 200 ng/mL predicted Srel to 2.5 (95% P.I: 1.2–4.8). Based on ROC analysis, the optimal discrimination threshold for CPSE concentration for Srel ≥ 2.5 was estimated as 90 ng/mL (95% confidence interval: 50–140), with a sensitivity of 85% and a specificity of 72%. Screening for CPSE is of potential value in the aging intact male dogs. Although many dogs with an Srel ≥ 2.5 show no clinical signs, the insidious nature of BPH supports further investigations of the prostate in these dogs, corresponding to a CPSE concentration of approximately 90 ng/mL or higher.

Introduction

Dogs live long lives, and median longevities exceed 10 years for several breeds [1]. With increased longevity, the quality of life at older age becomes more important. BPH affects an increasing proportion of intact male dogs with advancing age [2], but is often clinically unnoticed [3], [4], [5]. In beagles 1–3 years old, 25% had hyperplastic prostates and the corresponding figure in the age group 5–10 years was 88% [6]. In another study, the prevalence increased to almost 100% after six years of age [7]. The pathologic features changes with age, from a glandular to a complex form [2]. The definition of BPH varies, and is based on histology, an increase in prostatic volume, or an increased in volume together with clinical signs [6], [8], [9], [10]. When clinical signs are detected, they may include signs related to the genitourinary tract (including sanguineous urethral discharge and decreased fertility), the gastrointestinal tract (e.g. constipation and dyschezia), lameness, and systemic signs such as anorexia [3], [4], [9], [11], [12]. However, clinical signs are not always present in dogs with histopathological changes of BPH, and, when present, they may go unnoticed by the owners, at least initially.

The etiology and pathophysiology of BPH is not fully clarified, but the condition is androgen dependent, and dihydrotestosterone appears to play a major role [2], [13], [14]. BPH can be induced experimentally in dogs by a combined treatment with androgens and estrogens [15]. The histopathological changes in experimentally induced disease and the naturally occurring disease are identical [6]. The androgen receptor (AR) is expressed in epithelial cells of both normal and hyperplastic tissue [16], and the expression of the AR and the estrogen receptor (ER) α decreases when the hormonal influence is withdrawn [17].

Diagnosing BPH is challenging. Hyperplasia is a histologic term, and when BPH is defined as “a large prostate with histologic verification of hyperplasia and no other histologic lesion” [9], or “obvious increase in the amount of secretory epithelium” [6], this necessitates a biopsy for histology, that can be considered the gold standard to diagnose BPH in the living animal. However, this is not a routine procedure in clinical practice. Others describe BPH merely as an age-related increase in prostate volume and weight [10]. In the clinic, the diagnosis is usually based on clinical signs in combination with an enlarged prostate. Determining the size is thus an important step in BPH investigations, but it should be kept in mind that dogs may have prostates of varying sizes without clinical signs [18]. The size of the prostate may be approximated through transrectal digital examination. The method has low sensitivity [5]; often only the caudal part of the prostate is reached. The procedure may be particularly difficult in both small and large breeds, but it allows investigation of e.g. asymmetry and consistency, and is valuable for detecting prostatic pain. Ultrasonography is often the method of choice for determining prostatic size [19], [20]. The method has the additional advantage of showing the internal parenchyma, allowing visualization of e.g. mineralization and cyst-like lesions, and evaluation of echogenicity and echotexture [18], [21], [22]. A drawback is the need for advanced equipment and trained personnel [23].

In addition to measures of prostatic size, circulating biomarkers may be of benefit for examination of prostatic status. Canine prostate specific esterase (CPSE) is an arginine esterase and the major secretory product of the canine prostate [24]. CPSE is regulated by testosterone and the activity of CPSE decreases when testosterone concentrations decline [25]. Serum CPSE activity has been described to be significantly higher in dogs with BPH than in normal dogs [26], [27], but a difference in concentrations between dogs with BPH, bacterial prostatitis or prostatic carcinoma has not been shown [26]. CPSE is thus a potentially valuable biomarker, and its use has been suggested in the diagnostic workup of dogs with clinical signs of BPH and for screening of geriatric dogs [28]. Still, information about the clinical use of CPSE is scarce.

The primary aim of the present study was to study the association between the concentration of the circulating biomarker CPSE and prostate volume. Secondary aims were to study associations between CPSE concentration and dog age and weight, ultrasonographic appearance of the prostate, and clinical signs of BPH. In addition, the associations between the prostate volume and dog age and weight, ultrasonographic appearance of the prostate and clinical signs of BPH were investigated.

Section snippets

Study design

Owners of male dogs were invited to participate with their dogs in the study. Written information was distributed via e-mail to veterinary students and university employees, and also via internet (using a facebook account of the university), and directly to dog owners visiting the participating hospitals and clinics. Dogs from two animal hospitals and two animal clinics were included. Breed, age, and weight were recorded. Anamnestic information on clinical signs of possible prostatic disease

The prostatic size was associated with CPSE concentration and with number of cysts

The median volume of the prostate was 22 cm3 (IQR 13–32 cm3). The median Srel was 1.9 (IQR 1.4–2.8). Seventy-five dogs in the present study had an Srel > 1. The median CV for prostatic length, width and height was <5% (IQR 1.1–4.6%). The maximum CV achieved was <15%.

The six dogs with clinical signs indicative of prostatic disease had Srel ≥ 2.5 (Fig. 1). In total, 26 of the dogs (33%) had a prostate with an Srel ≥ 2.5. Log concentration of CPSE (P < 0.001) and presence of more than five cysts

Discussion

Diagnosing BPH is challenging, and it can be assumed that nearly all intact male dogs will develop histopathologic BPH if they live long enough. The diagnosis of clinical BPH is usually based on typical clinical signs together with prostatic enlargement. However, the size of the prostate varies widely among dogs without clinical signs [18], which was also seen in the present study. Reliable estimates of prostatic volume can be achieved with ultrasonography, but this requires both costly

Conclusion

Circulating concentrations of CPSE were associated to relative size of the prostate and analysis of CPSE may be valuable in the screening of geriatric intact male dogs and in the work up of BPH. A higher cutoff than generally recommended by the manufacturer for the diagnosis of BPH is advisable for determining an increase in prostatic size of 2.5 or more in dogs ≥ four years.

Acknowledgments

The skilled technical assistance by Annlouise Jansson is greatly acknowledged. The authors thank Dr. Sofie Ödling at Evidensia Specialist Animal Hospital Strömsholm, Sweden, for contribution of cases. Virbac kindly supported the study with Odelis CPSE™ ELISA kits. The study was financially supported by the Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.

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