Effect of the addition of estrogen to medical castration on prostatic size, symptoms, histology and serum prostate specific antigen in 4 men with benign prostatic hypertrophy.

A total of 4 men with benign prostatic hypertrophy who underwent medical castration therapy with a long-acting gonadotropin-releasing hormone agonist (leuprolide) for more than 6 months elected to add an estrogen transdermal patch (0.05 mg. to the skin biweekly) to the leuprolide regimen. The average prostatic size (transrectal ultrasound), serum prostate specific antigen (PSA) levels and symptoms of prostatism were dramatically decreased with leuprolide alone. The addition of estrogen for 6 months did not result in any change in prostate size, symptoms or serum PSA levels over that seen with leuprolide alone. The development of squamous metaplasia was noted in 1 man with leuprolide alone and in 1 man after the addition of estrogen. Immunohistochemical staining with anticytokeratin 903 antibodies reveals that squamous metaplasia appears to arise from prostatic basal cells. We postulate that the target cell for estrogen action in the prostate is the prostatic basal cell. In the absence of androgen the only direct effect of estrogens is the induction of squamous metaplasia.     

Changes of phenotypic expression of prostatic antigen in secondary transitional cell carcinoma of the prostate: evidence for induction phenomenon as a mechanism for acquisition of prostatic antigens in prostatic transitional cell carcinoma

BACKGROUND: In vitro and experimental studies of mesenchymal-epithelial interaction for the prostatic stroma have demonstrated that the prostatic stroma is capable of inducing the nonprostatic epithelium to acquire many features of prostatic epithelium. We investigated whether this phenomenon could be observed in vivo in human prostatic stroma. MATERIALS AND METHODS Sixty transitional cell carcinoma (TCC) of the urinary bladder: (a) 20 with glandular lumen; (b) 20 without glandular lumen: (c) 10 mixed TCC-adenocarcinoma (ACA); and (d) 10 with synchronous or metachronous TCC of the prostate; and three primary TCC of the prostate were examined and submitted for immunostaining for prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA). RESULTS: There was a spectrum of immunostaining for PSA ranging from negative reactivity in TCC without glandular lumen of the urinary bladder, to focal and weak reactivity in single cells with varying degrees of nonmucinous glandular differentiation and to strong reactivity in groups of cells in primary and synchronous or metachronous TCC in the prostate. The areas of carcinoma geographically closest to the prostate and with the most extensive nonmucinous glandular differentiation displayed the most frequent and strongest immunoreactivity for PSA. The immunoreactivity for PAP was usually stronger than for PSA. Four cases of TCC and mixed TCC-ACA were immunoreactive only for PAP. Furthermore, there was a change in the phenotype of TCC in the urinary bladder as it spread into the prostate. For 10 TCC in the urinary bladder with synchronous or metachronous tumor in the prostate, all TCC in the urinary bladder were negative for PAP and PSA, whereas six TCC in the prostate were focally positive. CONCLUSIONS: The spectrum of immunoreactivity for PAP and PSA and the change in immunoreactivity of TCC of the urinary bladder as it spreads into the prostate are likely induced by the prostatic stroma through the mechanism of mesenchymal-epithelial interaction. Prostate 47:172-182, 2001.     

Immunohistochemical demonstration of tumor-associated antigens in prostatic carcinomas of various histological differentiations

Prostate acid phosphatase (PAP), prostate-specific antigen (PSA), carcinoembryonic antigen (CEA) and keratin were determined immunohistochemically in paraffin sections from 64 prostatic carcinomas fixed in formalin according to the conventional method. The results obtained with PSA led to the correct diagnosis of prostatic carcinoma in 90.7% of the cases. 80.3% of the diagnoses obtained with PAP were correct. The intensity of the staining of the marker decreased with increasing differentiation. 3 utricular carcinomas were positive for PAP and PSA. CEA and keratin may be considered unspecific tumor markers only. However, metaplastic squamous epithelium from poorly differentiated carcinomas was always positive for keratin. PAP and PSA are also suitable for differentiating between tumors of prostatic and nonprostatic origin and could thus be successfully used to determine immunohistochemically the histogenesis of 15 invasive, poorly differentiated carcinomas of the prostate and bladder. PSA again proved to be a more specific epithelial marker than PAP.     

PAP and PSA in prostatic carcinoma cell lines and aspiration biopsies: relation to hormone sensitivity and to cytological grading

Because a change from hormone-sensitive to hormone-resistant carcinoma of the prostate often occurs concomitantly with genetic changes or as a result of the latter, the markers specific for prostatic tissues might also be affected. We therefore first studied the presence of prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) in LNCaP and LNCaP-r human prostatic carcinoma cell lines. Since both markers were found in these cell lines, we proceeded to quantitate PAP and PSA in aspiration biopsies from patients with prostate tumors. The amounts of these markers were compared with cytological findings. PAP and PSA were analyzed in the biopsy material from 120 patients using commercial radioimmunoassay (RIA) kits. DNA was determined using Riedel H33258 stain. Cytological grading was performed according to the Uropathological Study Group of Prostatic Carcinoma. Significant correlations were found between PAP/DNA or PSA/DNA values and grade of differentiation of the prostate tumor. In view of earlier reports and the results presented here, the amounts of markers or the protein pattern of tumor tissue may be a useful complement to the morphological findings and for selecting optimal therapy for patients with prostatic tumors.     

Regulation of prostatic carcinoma cell proliferation and secretory activity by extracellular matrix and stromal secretions.

Previous studies from our laboratory have shown that reconstituted basement membrane and stromal secretory products are important regulators of benign prostatic epithelial cell growth and differentiation. In the present study we evaluated the impact of extracellular matrix (ECM) and soluble stromal secretory products on the proliferation and secretory activity of the androgen-responsive prostatic carcinoma cell line LNCaP. In these studies, dihydrotestosterone (DHT) was a potent mitogen for LNCaP cells cultured on plastic or on type I collagen. The growth response to DHT was greatly attenuated when LNCaP cells were grown on prostatic stromal ECM. Cells grown on stromal ECM also exhibited clustered morphology compared to the monolayer growth observed on plastic and secreted elevated levels of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). These findings indicate that cultivation of LNCaP on stromal ECM will promote the expression of differentiated functions. In additional studies, stromal cell conditioned medium (SCM) significantly increased PSA/PAP secretion by LNCaP cells in the presence of 10 nM DHT. The enhancement of DHT-induced PSA/PAP secretion by SCM was most pronounced when LNCaP cells were grown on stromal ECM. SCM did not significantly alter LNCaP proliferation. These studies indicate that prostatic stromal ECM and soluble secretory products will promote differentiated function in cultured LNCaP cells. In addition, we show that DHT can act as either a growth or differentiation-promoting stimulus depending on the presence of stromal factors.     

Unusual morphologic patterns of basal cell hyperplasia of the prostate.

The distinction of basal cell hyperplasia (BCH) from carcinoma or high-grade prostatic intraepithelial neoplasia may be difficult. We reviewed 25 cases of BCH with unusual features and identified four distinct groups: BCH with intracytoplasmic globules (five cases); BCH with calcifications (eight cases), including one with globules; BCH with squamous features (three cases); and cribriform BCH (nine cases), including two cases with globules. A total of five cases contained prominent nucleoli and/or cytologic atypia. Hyaline cytoplasmic globules have not been described in any other prostatic entity and appear diagnostic of BCH. Calcifications observed in BCH were psammomatous, differing from the fine stippled calcifications occasionally seen in areas of comedonecrosis within high-grade prostatic carcinoma. Basal cell hyperplasia with squamous features differed from squamous differentiation in carcinomas (adenosquamous carcinoma) and from benign foci of squamous differentiation seen associated with either prostatic infarcts or with hormonal therapy. Whereas cribriform prostatic intraepithelial neoplasia and cribriform cancer glands represent a single glandular unit with punched out lumina, many of the glands within a focus of cribriform BCH appeared as fused individual BCH glands. The use of cytokeratin 34betaE12 can help in difficult cases. In cribriform BCH high-molecular-weight cytokeratin shows multilayered staining of the basal cells in some of the glands and a continuous layer of immunoreactivity. Cribriform prostatic intraepithelial neoplasia demonstrates an interrupted immunoreactive single cell layer of basal cells. Recognition of the architectural and cytologic features of unusual morphologies of BCH can be used to facilitate its diagnosis and differentiation from prostatic carcinoma and high-grade prostatic intraepithelial neoplasia.     

ROLE OF PROSTATE-SPECIFIC ANTIGEN AND DIGITAL RECTAL EXAMINATION IN THE DETECTION OF PROSTATE CANCER

Prostate-specific antigen (PSA) is a kallikrein-like serine protease that is secreted exclusively by the epithelial cells of all types of prostatic tissue, benign and malignant. Its serum concentration is raised in men with prostatic disease including cancer. We have evaluated its usefulness in the diagnosis of prostate cancer by measuring serum PSA concentrations in 260 men aged 50 years or over. All had abnormalities at digital rectal examination (DRE) involving suspected cancer, signs and symptoms of benign prostatic hyperplasia and equivocal findings on DRE, and miscellaneous other conditions, including hematospermia, chronic prostatitis and microscopic hematuria. Transrectal prostatic needle biopsies were performed in the men with abnormal findings on DRE or elevated serum PSA (above 4ng/ml). Serum PSA ranged from 4.0 to 9.9ng/ml in 14 (5%) of the 260 men. Four of the men in this group (31%) who underwent prostatic biopsy had prostate cancer. Serum PSA levels greater than or equal to 10.0 ng/ml were found in 8 (3%) of the 260 men. 5 of these 8 (63%) who underwent prostatic biopsy had cancer. If DRE alone had been used to screen the men having biopsies, 4 of the 10 cancers (40%) would have been missed. If PSA alone had been used to screen these men, only 1 of the 10 cancers would have been missed. Serum PSA measurement was more reliable than DRE for detecting prostate cancer. Since these two methods do not always detect the same malignant tumor, the combined use of DRE and PSA testing affords a more complete evaluation of the prostate gland for malignant involvement.     

Detection of prostate specific antigen in pancreas and salivary glands: a potential impact on prostate cancer overestimation

Purpose

We explored the immunohistochemical expression of prostate specific antigen (PSA) in pancreas and salivary glands.

Materials and Methods

We investigated 62 specimens from male and female subjects, representing normal cases and several pathological conditions of pancreas and salivary glands. Two commercially available monoclonal antisera for PSA and 1 for prostatic acid phosphatase were used.

Results

A consistently positive reaction for PSA and prostatic acid phosphatase, independent of patient sex, was noted in ductal cells of normal pancreas and normal salivary glands, as well as pleomorphic adenoma, adenocarcinoma and all oncocytic epithelial cells of Warthin's tumor. Reaction was absent in normal stromal and acinar cells, and squamous carcinoma.

Conclusions

PSA is detectable in normal and cancer tissues far from the prostate. Therefore, we may not entirely rely on specificity of PSA alone to diagnose metastatic prostate cancer.     

Ectopic prostatic tissue in the uterine cervix and vagina: report of a series with a detailed immunohistochemical analysis

Prostatic tissue has rarely been described in the lower female genital tract. We describe 6 cases of ectopic prostatic tissue: 5 involving the cervix and 1 the vagina. The latter is the first reported example of benign prostatic tissue in the vagina. The age of the patients ranged from 21 to 65 years; and in all cases, the prostatic tissue was located within the cervical or vaginal stroma without involvement of the surface. In all cases, there were both glandular and squamous elements, which varied in prominence. In some cases, the squamous elements predominated to such an extent that the underlying glandular component was easily overlooked. In the glandular areas, a double cell layer of luminal and basal cells was focally apparent. There was little cytologic atypia or mitotic activity. Immunohistochemically, 3 of 6 cases were positive with prostate specific antigen (PSA) and all 6 cases marked with prostatic acid phosphatase (PSAP). In some of the positive cases, staining was focal. Positive staining with prostatic markers was confined to the glandular elements with no staining of the squamous areas. Immunohistochemical staining with the high molecular weight cytokeratin 34betaE12 highlighted the basal cell layer, which often extended into the center of the cellular islands, reminiscent of basal cell hyperplasia involving the prostate gland. All cases tested were CD10 positive (largely restricted to the basal cell layer), alpha-methylacyl-CoA racemase positive, and p16 negative. Estrogen receptor (ER) and progesterone receptor (PR) were negative in the glandular areas, but ER was positive in the squamous elements in all cases and PR was positive in 1 case. All cases tested were androgen receptor positive and exhibited a low MIB-1 proliferation index with only scattered positive nuclei. The presence of ectopic prostatic tissue in the lower female genital tract may be more common than is appreciated. Once the possibility is considered, the diagnosis is easily confirmed using immunohistochemistry, although staining with prostatic markers may be focal and PSA may be negative. Ectopic prostatic tissue in the lower female genital tract is almost certainly a benign condition, based on the morphology, including the presence of a double cell layer, although follow-up of larger numbers of cases is required. Possible theories of histogenesis include a developmental anomaly, metaplasia of preexisting endocervical glands, and derivation from mesonephric remnants.     

Inflammation in prostate biopsies of men without prostatic malignancy or clinical prostatitis: correlation with total serum PSA and PSA density

OBJECTIVE: Inflammation is a frequent histological finding in prostate biopsies, performed on men without prostatic malignancy or clinical prostatitis. We investigated the relationship between morphological parameters of inflammation in prostatic tissue and total serum prostate-specific antigen (PSA) and prostate-specific antigen density (PSAD) levels to determine if subclinical inflammation can cause elevation of PSA and PSAD. METHODS: We reviewed 268 prostate biopsies, performed on 238 men with elevated PSA and/or abnormal digital rectal examination of the prostate. All premalignant and malignant biopsies and cases of clinical prostatitis were excluded. The inflammation in the remaining 145 prostate biopsies was scored for extent of inflammation and aggressiveness of inflammation, using the four-point scale designed by Irani and co-workers. In this prostatic inflammation scoring system, extent of inflammation is graded from 0 up to 3 according to the degree of invasion of inflammatory cells in prostatic tissue. Aggressiveness of inflammation is graded from 0 up to 3 according to the degree of contact or disruption of prostatic glandular epithelium by inflammatory cells. RESULTS: Each of the studied biopsies showed inflammatory cells. Median PSA levels in grades 1, 2 and 3 of extent of inflammation were, respectively, 5.7, 6.8 and 13. 0. Median PSAD levels in these groups were 0.13, 0.16 and 0.33. There was no significant difference between these grades for PSA nor for PSAD. Median PSA levels in grades 0, 1 and 2 of aggressiveness of inflammation were, respectively, 3.9, 5.9 and 8.9. Median PSAD levels in these groups were 0.12, 0.18 and 0.17. For both parameters, there was a significant difference between grades (respectively, p = 0.0028 and p = 0.0330). CONCLUSION: Inflammation of the prostate is a histological finding in almost every set of prostate biopsies, even when there are no signs of clinical prostatitis. This subclinical inflammation can cause PSA elevation. Not the extent of inflammation is of importance, but the disruption of epithelial integrity caused by the inflammatory infiltrate. When confronted with a patient with an elevated PSA level whose prostate biopsies reveal no malignancy but only inflammation, this concept can help in determining the need for quick repeat biopsies.     

Regulation of prostate-specific antigen gene expression in LNCaP human prostatic carcinoma cells by growth,dihydrotestosterone, and extracellular matrix

We have examined the role of extracellular matrix (ECM), cell growth, and dihydrotestosterone on the expression of prostate-specific antigen (PSA) by human prostatic carcinoma cells LNCaP. ECM induced a transient decrease in PSA mRNA even in the presence of growth factors. PSA mRNA, but not actin mRNA, was down-regulated on ECM in a biphasic manner and was not detected up to 48 hr after culture, but was re-expressed after 3 days. Cycloheximide and actinomycin D pretreatment did not prevent ECM-induced down-regulation of PSA mRNA, while actinomycin D-treated cells on plastic maintained stable PSA mRNA levels. DNA synthesis and PSA glycoprotein secretion were also transiently suppressed on ECM. LNCaP growth inhibition correlated with decreased glyceraldehyde phosphate dehydrogenase mRNA levels. However, the transient growth suppression induced by ECM was not observed with primary endothelial cells on Matrigel. Down-regulation of PSA mRNA by culture on Matrigel was reversible upon transfer to a different matrix substrate. Re-expression was highest on heparan sulfate proteoglycan (4-fold) and fibronectin or collagen I (2-fold) compared to plastic or laminin. Our results indicate that the morphology and proliferation of LNCaP cells may be regulated by the ability of ECM to control cellular differentiation and proliferation. © 1994 Wiley-Liss, Inc.     

Cells in various benign and malignant conditions of the human prostate express different antigenic phenotypes

Prostatic epithelium basically consists of secretory-luminal, basal and endocrine-paracrine cells. Immunohistochemical procedures are frequently used for showing the cells reflecting different differentiations. In this study, 40 prostatic tissue specimens submitted to the Department of Pathology of Inönü University, Research Hospital, between 1991 and 1996 were examined. Half of the cases were diagnosed as cancer and the other half had various benign lesions. Of the cases 22.5% (n=9) were needle biopsy material whereas the remainder, 47.5% (n=19), were from prostatectomy and 30% (n=12) were transurethral resection of the prostate (TURP) specimens. High molecular weight anti-cytokeratin antibodies (HMW anti-cytokeratin) stained basal cells both in all normal prostatic tissue and benign prostatic lesions, but in the majority of cancers (70%, n=14) negative immunoreactivity was seen. Nevertheless, in some of the cancer cases (30%, n=6) basal cell anti-cytokeratin staining was shown. Negative immunoreactivity with HMW anti-cytokeratin is important in distinguishing between malignant and benign lesions, whereas positive staining is not every time in favour of benign lesions. With the usage of prostate specific antigen (PSA) it was seen that all of the malignant and benign prostatic lesions stained positively. Basal cells in hyperplastic glands were not stained with this stain. Irregular, and in some areas, intense (PSA) immunoreactivity is present in precancerous and malignant lesions. Endocrine cells, which are represented with Chromogranin-A (Chr-A) immunoreactivity and reflecting neuroendocrine differentiation, are present in 75% (n=15) of benign lesions and in 50% (n=10) of cancer cases. It was thought that the lesser number of these cells in neoplastic lesions in comparison to the non-tumoral lesions is correlated with the disorder of mechanism that regulates the cell growth. Both in neoplastic and non-tumoral tissues the prostatic epithelial cells showed the three markers, namely HMW anti-cytokeratin, PSA, and Chr-A, which may reflect the multidirectional differentiation of these cells from a pluripotent origin.     

Studies on the differentiation pathway and growth characteristics of epithelial culture cells of the human prostate

We established explant primary cultures in order to study the growth and hormone responsiveness, and the differentiation process of prostatic epithelial cells. Cell outgrowth was achieved from explant tissue by using a new DU145-cell-conditioned medium and special plastic coverslips. To define the present model, proliferation assays were tested by [3H]thymidine assay and planimetric analysis. Cells were analyzed using immunocytochemistry, light, phase contrast and electron microscopy, polymerase chain reaction, telomerase ELISA and immunoassay (PSA). Morphology and electron microscopy revealed typical epithelial differentiation. Immunocytochemistry showed the content of basal and secretory epithelial cells, endocrine paracrine cells and a high level of proliferation. With increasing culture time, mature epithelial differentiation (PSA) increases and the initial increase of alpha-smooth muscle actin (alpha-SMA) decreases again. After further passaging, alpha-SMA expression is no longer detected and PSA expression decreases. Furthermore, epithelial cells showed both androgen responsiveness and androgen receptor expression. These findings show the presence of epithelial cells in a process of differentiation with endocrine paracrine cells and a high level of proliferation. This model may maintain the cellular and functional properties more closely related to the human prostate and may provide a valuable tool for studying stem cells and differentiation characteristics.     

Excretion of three major prostatic secretory proteins in the urine of normal men and patients with benign prostatic hypertrophy or prostate cancer

We have studied the mode of excretion of three prostatic secretory proteins, namely acid phosphatase (PAP), prostate-specific antigen (PSA) and beta-inhibin, in the urine of normal adult men, and we have determined the urinary levels of these proteins in men with benign prostatic hypertrophy (BPH) or adenocarcinoma. The output of the three proteins was highly variable during the day. In order to minimize these variations, 24-hour urine samples were collected thereafter. Our study showed that PAP concentrations in 50% of men with or without symptomatic BPH were similar to those of normal young men. In the remaining 50%, PAP was undetectable. In contrast, average PSA and beta-inhibin concentrations were higher in patients with BPH than in young men (p less than 0.05). The three markers were decreased or nondetectable in about half of the patients with untreated prostatic cancer. This phenomenon was even more pronounced in patients receiving hormonal treatment (castration or diethylstilbestrol). However, some of these patients still excreted normal amounts of PAP, PSA, and beta-inhibin. Urinary and serum PAP levels showed no correlation. These results indicate that urinary prostatic markers provide an easy means to study the behavior of the primary prostatic tumor. This information may be of potential value since it is not obtained with serum markers which originate mostly from metastatic cells.     

Prostatic calculi do not influence the level of serum prostate specific antigen in men without clinically detectable prostate cancer or prostatitis

PURPOSE: Prostatic calculi are common but little is known of their effect on serum prostate specific antigen (PSA). We investigated whether prostatic calculi might influence serum PSA in men with clinically undetectable prostatic cancer or prostatitis. MATERIALS AND METHODS: Between November 1999 and November 2001, 581 consecutive patients underwent serum PSA determination and digital rectal examination. Of these patients 486 without detectable prostatic cancer, or a history or symptoms of prostatitis and with other specified exclusion criteria were included in the study. The detection and volume measurement of prostatic calculi, and the measurement of prostate volume were performed by transrectal ultrasonography. RESULTS: Prostatic calculi were detected in 198 of the 486 men (40.7%). Mean patient age, prostate volume and serum PSA were not significantly different in men with and without prostatic calculi. Prostate volume was significantly greater in patients with abnormally elevated serum PSA than in those with normal levels. However, no significant difference was found between the percent of men with prostatic calculi or the volumes of prostatic calculi in the 2 groups. Univariate logistic regression analysis indicated that the presence or volume of prostatic calculi was not a risk factor for elevated PSA. Multivariate analysis showed that age and prostate volume were associated with elevated PSA. CONCLUSIONS: The presence or volume of prostatic calculi had no significant effect on serum PSA. Our results suggest that the influence of prostatic calculi is irrelevant in men with elevated PSA.     

Prostate-specific antigen in the follow-up of prostatic adenocarcinoma treated with external beam radiation.

Prostate-specific antigen (PSA) has been shown to be a more sensitive tumor marker than prostatic acid phosphatase (PAP) in prostatic adenocarcinoma: PSA was positive in 54 of our 117 patients (46%) and PAP was positive in 24 (21%). In order to compare the usefulness of these markers during and after radiotherapy serum samples from 24 patients treated with external beam irradiation were analyzed. PAP was only slightly positive in 1 patient (4%) after radiotherapy. His PSA level was highly elevated and he died of progressive disease. In the other 23 patients the cancer was in local control. However, the serum PSA level remained positive in 5 of these patients indicating vital cancer cells may still have been present. An alternative possibility is that metaplastic prostatic cells which secrete PSA were left after radiotherapy, as has been shown to be the case in prostatic hyperplasia. Before radiotherapy increased PSA levels were measured in 3 patients. In 2 of them the level declined to normal within 6 months after radiotherapy. The PAP levels were normal. It is concluded that PSA (positive in 25% of patients after radiotherapy) might be more sensitive than PAP (positive in 4%) in monitoring the effect of radiotherapy in prostatic cancer patients.     

Sclerosing adenosis of the prostate gland. A lesion showing myoepithelial differentiation.

Sclerosing adenosis of the prostate is a rare lesion characterized by the proliferation of variably sized glands in a cellular stroma. We report light microscopic, immunohistochemical, and ultrastructural studies in 22 examples from 15 patients. Two cases were identified in 100 consecutive prostates embedded by a whole organ method, giving a prevalence of 2%. Antibodies directed against the following antigens were used: high-molecular-weight cytokeratin (CKH; 34 beta E12); cytokeratin (CK; AE1/AE3), prostatic acid phosphatase (PAP), prostate-specific antigen (PSA), S-100 protein, muscle-specific actin (HHF35), and vimentin (Vim). Cells within the glandular component demonstrated positive reactivity for CK, CHH, PSA, and PAP, indicating a prostatic epithelial origin. In addition, a distinct population of cells reacting for muscle-specific actin and S-100 protein was identified within this glandular element. Adequate material for ultrastructural study was available in five cases; all showed the presence of flattened cells located between the basement membrane and secretory epithelial cells, which had features typical for myoepithelial differentiation. Although the prostate gland does not normally contain myoepithelial cells, we have documented their consistent presence in this unusual lesion; we believe these cells arise by a metaplastic process from the prostatic basal cells.     

Use of neuroendocrine serum markers in the follow-up of patients with cancer of the prostate

Neuroendocrine (NE) differentiation of prostatic adenocarcinomas has received increasing attention in recent years as a result of possible implications on prognosis and therapy. The incidence of NE cells in tumors has been reported from 10% up to 100%. Several studies have shown chromogranin A (CgA) to be the most reliable serum marker of NE differentiation. We have followed 22 patients with prostatic adenocarcinoma over a 2-year period. The patients underwent a palliative transurethral resection of the prostate (TURP) because of urinary outflow obstruction. The prostatic tissue specimens were stained immunohistochemically using antibodies against CgA, chromogranin B (CgB), neuron-specific enolase (NSE), thyroid-stimulating hormone (TSH), serotonin, and somatostatin. In addition, each specimen was stained with hematoxylin & eosin (H & E), and saffran for tumor grading. Blood samples were taken preoperatively and after 1, 3, 6, and 24 months. The serum values of CgA, CgB, pancreastatin (Pst), NSE, and prostate-specific antigen (PSA) were determined from each sample. Carcinomas with groups of CgA-positive cells had higher serum levels of CgA compared to carcinomas with no or only scattered CgA-positive NE cells. During the 2-year period, there were no statistical significant variations in serum levels of CgA, NSE, Pst, and PSA. However, there was a significant increase in serum levels of CgB during the same period. P = 0.002, possibly due to an increase in number of NE cells in tumor or to a relative increase in production of CgB in the NE cells. Prostate 31:110–117, 1997. © 1997 Wiley-Liss, Inc.