SLPI for Prostate Cancer

NCT ID: NCT04854343

Last Updated: 2022-05-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

280 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-12-01

Study Completion Date

2024-07-01

Brief Summary

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Exploratory study of SLPI expression in human prostate cancer patients This is a no-profit exploratory study about the expression of SLPI in human prostate cancer patients that will enroll about 200 patients admitted for suspect prostate cancer to Careggi University Hospital. We will verify whether an increase SLPI levels in the sera may serve as biomarker of cancer progression.

Detailed Description

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Prostate cancer (PC) is a heterogeneous disease that occurs more frequently in elderly men. Prostate cancer is usually localized and it has a slow progression; thus, the patient may not suffer from any symptom for years. However, a proportion of patients PC develops metastases and may become a clinically relevant disease that can show an aggressive behavior and, eventually, give metastases. In any event, since it is the most common male cancer in the Western countries, it is the second leading cause of cancer deaths in males. For this reason the identification of the molecular alterations determining the different clinical behaviors and of the associated biomarkers would be extremely useful.

The Secretory leukocyte protease inhibitor (SLPI) is a serine protease which best-defined function is to protect host tissues from the excessive damage by proteolytic enzymes released during inflammation. Recently SLPI has been found overexpressed in a variety of cancers (pancreatic, papillary thyroid, uterine cervix, endometrial, and ovarian cancer). In apparent contrast, SLPI has been found reduced in the sera (and tumor tissue) of prostate cancer patients in the respect of healthy subjects and of subjects with benign hyperplasia. However, SLPI has been found upregulated in castration resistant prostate cancer (CRPC) patients and in a subset of CRPC cell lines.

These data suggest that expression of SLPI in prostate cancer could be biphasic: underexpressed during the early stages and overexpressed during progression. This peculiar pattern of SLPI expression suggests that SLPI may play a role in prostate cancer pathogenesis and/or in determining its neoplastic features. In this respect, it is noteworthy that SLPI is located at 20q13.2 (HPC20 locus), a locus harboring prostate cancer susceptibility genes. Based on these data it is possible to hypothesize that prostate cancer progression could be associated, and possibly heralded, by the increase of SLPI.

This is an observational investigation of SLPI levels in blood and tissue samples of patients with prostate disease with the explorative goal to verify whether SLPI could be a potential biomarker of prostate cancer progression.

Conditions

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Prostate Cancer Prostatic Neoplasm

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Case

200 patients with a suspicion of prostate cancer

Secretory leukocyte protease inhibitor (SLPI) in prostate cancer

Intervention Type DIAGNOSTIC_TEST

7 ml of peripheral blood and a urine sample for the determination of SLPI concentration. Blood samples will be promptly processed to obtain sera; both sera and urine will be stored at -80°C in the laboratory. The levels of SLPI in the serum and in the urine will be quantitated by an ELISA assay by using the "Human SLPI Quantikine ELISA Kit". SLPI level will be measured at diagnosis and during the follow-up (3, 9, 15 months and in case of progression).

Immunohistochemistry protocol for SLPI immunostaining to investigate SLPI levels prostate tissue

Determination of molecular alterations

Intervention Type DIAGNOSTIC_TEST

The presence of ETS translocation (or of ETS overexpression) will be tested on bioptic samples in each patient as for routine diagnostic procedures. First, ERG overexpression will be investigated by ERG immunostaining. The samples negative for ERG immunostaining will be studied for TMPRSS2-ERG translocation either by in situ FISH or by a translocation-specific RT-PCR. Next, the biopsies negative for TMPRSS2-ERG will be tested for the overexpression of other ETS proteins (ETV1, ETV4, ETV5 and for others rarely occurring ETS). When possible, it will be determined the status of pTEN gene, the tumor suppressor most frequently lost in prostate patients. The patients negative for the overexpression of the ETS proteins will be tested for SPINK1.

Control A

(a) 50 patients with benign prostate hyperplasia (BPH)

Determination of molecular alterations

Intervention Type DIAGNOSTIC_TEST

The presence of ETS translocation (or of ETS overexpression) will be tested on bioptic samples in each patient as for routine diagnostic procedures. First, ERG overexpression will be investigated by ERG immunostaining. The samples negative for ERG immunostaining will be studied for TMPRSS2-ERG translocation either by in situ FISH or by a translocation-specific RT-PCR. Next, the biopsies negative for TMPRSS2-ERG will be tested for the overexpression of other ETS proteins (ETV1, ETV4, ETV5 and for others rarely occurring ETS). When possible, it will be determined the status of pTEN gene, the tumor suppressor most frequently lost in prostate patients. The patients negative for the overexpression of the ETS proteins will be tested for SPINK1.

Secretory leukocyte protease inhibitor (SLPI) Healthy

Intervention Type DIAGNOSTIC_TEST

SLPI level will be measured also in the serum and in the urine from controls (patients with BPH and healthy subjects).

7 ml of peripheral blood and a urine sample for the determination of SLPI concentration. Blood samples will be promptly processed to obtain sera; both sera and urine will be stored at -80°C in the laboratory. The levels of SLPI in the serum and in the urine will be quantitated by an ELISA assay by using the "Human SLPI Quantikine ELISA Kit".

Control B

(b) 30 male subjects older than 50 years with neither prostate disease nor any other neoplasia

Secretory leukocyte protease inhibitor (SLPI) Healthy

Intervention Type DIAGNOSTIC_TEST

SLPI level will be measured also in the serum and in the urine from controls (patients with BPH and healthy subjects).

7 ml of peripheral blood and a urine sample for the determination of SLPI concentration. Blood samples will be promptly processed to obtain sera; both sera and urine will be stored at -80°C in the laboratory. The levels of SLPI in the serum and in the urine will be quantitated by an ELISA assay by using the "Human SLPI Quantikine ELISA Kit".

Interventions

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Secretory leukocyte protease inhibitor (SLPI) in prostate cancer

7 ml of peripheral blood and a urine sample for the determination of SLPI concentration. Blood samples will be promptly processed to obtain sera; both sera and urine will be stored at -80°C in the laboratory. The levels of SLPI in the serum and in the urine will be quantitated by an ELISA assay by using the "Human SLPI Quantikine ELISA Kit". SLPI level will be measured at diagnosis and during the follow-up (3, 9, 15 months and in case of progression).

Immunohistochemistry protocol for SLPI immunostaining to investigate SLPI levels prostate tissue

Intervention Type DIAGNOSTIC_TEST

Determination of molecular alterations

The presence of ETS translocation (or of ETS overexpression) will be tested on bioptic samples in each patient as for routine diagnostic procedures. First, ERG overexpression will be investigated by ERG immunostaining. The samples negative for ERG immunostaining will be studied for TMPRSS2-ERG translocation either by in situ FISH or by a translocation-specific RT-PCR. Next, the biopsies negative for TMPRSS2-ERG will be tested for the overexpression of other ETS proteins (ETV1, ETV4, ETV5 and for others rarely occurring ETS). When possible, it will be determined the status of pTEN gene, the tumor suppressor most frequently lost in prostate patients. The patients negative for the overexpression of the ETS proteins will be tested for SPINK1.

Intervention Type DIAGNOSTIC_TEST

Secretory leukocyte protease inhibitor (SLPI) Healthy

SLPI level will be measured also in the serum and in the urine from controls (patients with BPH and healthy subjects).

7 ml of peripheral blood and a urine sample for the determination of SLPI concentration. Blood samples will be promptly processed to obtain sera; both sera and urine will be stored at -80°C in the laboratory. The levels of SLPI in the serum and in the urine will be quantitated by an ELISA assay by using the "Human SLPI Quantikine ELISA Kit".

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Patients with prostate carcinoma.
* Patients with Benign Prostatic Hyperplasia.
* Male subjects older that 50 years without prostate or neoplastic diseases.

Exclusion Criteria

* Male subjects younger that 50 years without prostate disease.
* Male subjects with neoplastic diseases either than prostate.
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Istituto per lo Studio, la Prevenzione e la Rete Oncologica

OTHER

Sponsor Role collaborator

Azienda Ospedaliero-Universitaria Careggi

OTHER

Sponsor Role collaborator

University of Florence

OTHER

Sponsor Role lead

Responsible Party

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Simone Morselli

PhD Student

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Rosario Notaro, MD

Role: PRINCIPAL_INVESTIGATOR

ISPRO

Locations

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Careggi University Hospital

Florence, Tuscany, Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Silvia Benemei

Role: CONTACT

055 7946999

Facility Contacts

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Simone Morselli, MD

Role: primary

3473050852

Sergio Serni, Prof

Role: backup

Other Identifiers

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17931

Identifier Type: -

Identifier Source: org_study_id

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