Prostate path
What are some genetic factors that can lead to prostatic adenocarcinoma pathogenesis?
-CAG repeats (on AR gene): short CAG repeats→ ↑sensitivity to androgens (African Americans > Caucasians > Asians) Inherited Polymorphisms -e.g. BRCA2 mutations: 20 fold increased risk -e.g. 8q24: increased risk in African Americans Somatic Mutations TMPRSS2 promoter-ERG/ETV1gene fusion -30-49% of patients treated by prostatectomy -can detect fusion genes in urine -increased ERG/ETV1 makes normal cells more invasive by increasing matrix metalloproteases Epigenetic Alterations -Hypermethylation of GSTP1 -Other genes silenced: PTEN, RB, p16/INK4a, MLH1, MSH2, APC
What are the variants of prostatic carcinoma?
-Ductal (aggressive, central/periurethralducts) -Mucinous -Small cell (most aggressive) -Other ---Mesenchymal neoplasms ---lymphoma Tumors metastatic to the prostate -Urothelial carcinoma (most common)
What is prostatitis?
An inflammation of the prostate that can be either acute or chronic Presents with a warm, tender, enlarged prostate Frequently sympomatic with: -dysuria -Increased urinary frequency and urgency -Lower back pain Acute: --often bacterial, such as e coli Chronic: -Bacterial or abacterial
What is the pathogenesis of Benign prostatic hyperplasia?
As men age, aromatase and 5a-reductase activity increase --aromatase converts androgen into estrogen --5a reductase converts androgen into DHT This increased metabolism leads to: -decdreased testosterone -Increased DHT and restrogen Estrogen leads to growth of cells in the prostate and DHT is anabolic to increase overall prostate size --Stromal tissue predominates, but glandular also grows --Median and lateral lobes usually enlarged, anterior seldom enlarged ----TZ is primary area of growth
What are the basic characteristics of benign prostatic hyperplasia?
Common in men > 50 yaers old Characterized by smooth, elastic, form nodular enlargement (hyperplasia and hypertrophy) of periurethral (lateral and middle) lobes of the prostate which compress the urethra into a vertical slit NOT premalignant Often presents with increased urinary frequency, nocturia, difficulty starting and stopping urine stream, and dysuria May lead to distesnion and hypertrophy of the bladder, hydronephrosis, UTI's, and an increased PSA Treatment: -A1 antagonist (terazosin, tamsulosin), which cause relaxation of smooth muscle -5a reductase inhibitors (finasteride) -Tadalafil
What are the basic characteristics of prostatic adenocarcinoma?
Common in men > 50 years old Arises most often from the posterior lobe (Peripheral zone) of the prostate gland and is most frequently diagnosed by increased PSA and subsequent needle core biopsy Prostate acid phosphatase (PAP) and PSA are useful tumor markers Osteoblastic metastases in bone may develop in late stage, as indicated by lower back pain and increased serum ALP and PSA
What are the components of normal prostate on histology
Composed of Acini for secretion and an outer basal cell layer that makes up the stroma The epithelium is composed of mostly secretory pseudostratified columnar epithelium, with some areas of squamous and transitional epithelium near the ducts
What is the normal cut off for a PSA? Why is this not effective? What are the adjusted age-specific ranges?
Cut off: 4 ng/ml --20-40% of patients with organ confined prostatic CA have a PSA value of 4 ng/ml or LESS Upper age-specific reference ranges (ng/ml): 40-49y: 2.5 50-59y: 3.5 60-69y: 4.5
What are the characteristics of High-Grade prostatic intraepithelial Neoplasia (HGPIN)
Inner secretory cells within an acinus/gland that have features of carcinoma However, the gland still has the out basal cells believed to precede the development of prostate adenocarcinoma -somewhere between normal and carcinoma recommended to follow up with a PSA
What is the lymph drainage of the prostate? What is the veinous drainage?
Lymph: ---Internal iliac lymph node cluster Venous: The prostatic venous plexus drains into the internal iliac vein which connects with the vertebral venous plexus, this is thought to be the route of bone metastasis of prostate cance This then drains into the internal iliac vain
What are the treatment methods for BPH?
Medical --5a reductase inhibitors --1a selective antagonist Surgery: -Simple prostatectomy -Transurethral resection
What are the histologic characteristics of prostatic adenocarcinoma
Often has more glandular tissue with cellular atypia to include: *Absence of basal cells* Prominent nucleoli
PSA is ____________ specific, not ____________ specific Its normal function is a ________________ that _________________ It is often increased in _________________, ________________, _______________ and ______________
Organ specific, not cancer specific Serine protease that cleaves seminal coagulum Prostatic carcinoma, Nodular hyperplasia,infection/inflammation, Infarction/instrumentation
What type of incontinence is often seen with Benign prostatic hyperplasia and how is it treated?
Overflow incontinence This is where incomplete emptying, due to outlet obstruction, leads to leaks with overfilling, and more post void residual urine (urinary retention) Treat with catheterization in patient, or with an alpha blocker such as Tamsulosin that selects for the area
What are the important characteristics of Free PSA?
PSA is normally bound to Alpha 1-antichymotrypsin in the blod Its calculated as the Free PSA/Total PSA x 100 in prostate CA, it is decreased, and often less than 10 % If it is greater than 25 > , the patient is at low risk
What is the grading system for Prostatic adenocarcinoma?
Primary Tumor: *T1: Clinically inapparent tumor* (DRE or TRUS) T1a: <5% of tissue resected T1b: >5% of tissue resected T1c: tumor identified by needle biopsy *T2: Tumor confined within the prostate* T2a: involves one lobe (<50%) T2b: involves one lobe (>50%) T2c: involves both lobes *T3: extends through prostatic capsule* T3a: extracapsular extension (unilateral or bilateral) T3b: tumor invades seminal vesicle(s) *T4: Fixed or invades adjacent structures other than seminal vesicle(s)*
What are the two most useful tumor markers for prostatic adenocarcinoma
Prostatic acid phosphatase and prostate-specific antigen (PSA) ---PSA total increases, but the fraction of free PSA decreases with adenocarcinoma
Prostate cancer is ranked _______________ in cancers for Men for incidence, and ____________ for mortality It commonly Metastasis to the ______________ , specifically the _______________, and is ________________ in nature
Ranked number one in incidence and number 2 in mortality Commonly metastasizes to the bone, specifically The axial skeleton It is blastic in nature, meaning that i creates MORE cells inside that area, making it more dense
What are the clinical features of BPH?
Symptoms result from compression of urethra by the nodules Obstructive symptoms: Difficulty voiding, hesitancy, nocturia and frequency Obstructive complications: Increased residual urine-infection, overflow incontinence, VUR, hydronephrosis, acute urinary retention
Translocation in the _______________ zone of the____________ gene, which leads to ______________ can often lead to an increased risk of prostatic adenocarcinoma This is because this gene zone is a __________________ , and its product can lead to an increased matrix metalloproteases, thus increasing ______________
TMPRSS2 Promoter ERG/ETV1 Leads to gene fusion This gene zone is an an androgen regulated promoter It makes normal cells more invasive
What is The Gleason grading system?
The grading system for prostatic adenocarcinoma it is the most powerful independent predictor of pathologic stage and survival in prostate cancer It is used with two scores during biopsy -First score is predominant pattern -Second score is other patterns seen ---biopsy cannot distinguish between 3 and 2, so lowest reported is 3 *Thus 5 + 3 is worse than 3 + 5) Well differentiated = --6 or lower Moderately differentiated = 7 Poorly differentiated = 8-10
What are the zones of the prostate?
The peripheral zone ---makes up 70 % of the prostate in young men The central zone ---approximately 25 % normally Transition zone ---5 % at puberty Anterior fibro-muscular zone (or stroma) ---Approximately 5 % total
What is meant by PSA velocity?
The rate of change/rise in serum PSA over a set amount of time Often greater in carcinoma than in benign conditions If PSA velocity is above a cut off value (0.75 ng/ml per year) it may mean prostatic adenocarcinoma even if the most recent PSA is less than the upper limit of normal
What are the characteristics of the Peripheral zone (PZ) of the prostate?
The sub-capsular portion of the posterior aspect of the prostate gland that surrounds the distal urethra. It is from this portion of the gland that ~70-80% of prostatic cancers originate
What are the characteristics of the Anterior fibromuscular zone (or stroma) of the prostate?
This zone is usually devoid of glandular components, and composed only, as its name suggests, of muscle and fibrous tissue. It is the portion you can normally feel through the rectum
What are the characteristics of the Central zone (CZ) of the prostate?
This zone surrounds the ejaculatory ducts. The central zone accounts for roughly 2.5% of prostate cancers although these cancers tend to be more aggressive and more likely to invade the seminal vesicles.
What is meant by perineural invasion?
Where a cancer is observed spreading to the space surrounding a nerve. It is common in head and neck cancer, prostate cancer and colorectal cancer.
What are the characteristics of the Transition zone (TZ) of the prostate?
~10-20% of prostate cancers originate in this zone . The transition zone surrounds the proximal urethra and is the region of the prostate gland that grows throughout life and is *responsible for the disease of benign prostatic enlargement*
What is the etiology and characteristics of prostatic adenocarcinoma?
•Most common cancer in males •9% of cancer related deaths in US •Wide range in behavior (aggressive to clinically insignificant cancer) •Majority are low-stage and low -grade Incidence: -<50y:<1%; >70y:>/= 70% -In US, Blacks>Whites; Americans>Asian •Clinical features: -Most are asymptomatic at diagnosis -5-20% have or develop distant spread and have symptoms due to metastasis (bone pain)
What is prostate-nodular hyperplasia?
•Multinodular proliferation of both stroma and glands •No known malignant potential Incidence: -Increases with age (25% by age 50y, and >50% by age 70y) -Blacks > Whites
What is the therapy for prostatic adenocarcinoma?
•Therapy: -Localized disease:surgery/radiotherapy or if low-grade "watchful waiting" -Advanced, metastatic disease: endocrine therapy (orchiectomy/estrogen/synthetic agonists of LH-RH)
