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IHC single marker with reporting - NKX 3.1, FFPE Tissue
Cancer
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IHC Single Marker with Reporting - NKX 3.1 FFPE Tissue
- Why is it done?
- NKX3.1 is a prostate-specific transcription factor used to identify and characterize prostatic tissue and differentiate benign prostatic epithelium from malignant prostate cancer
- Used for diagnosis and classification of prostate adenocarcinomas and metastatic prostate cancer in tissue biopsies and surgical specimens
- Assists in confirming prostatic origin of tumors, particularly in identifying poorly differentiated adenocarcinomas and atypical lesions
- Helps differentiate benign prostatic hyperplasia (BPH) from adenocarcinoma and supports grading of prostate cancer
- Performed on formalin-fixed, paraffin-embedded (FFPE) tissue sections obtained from prostate biopsies, prostatectomy specimens, or tissue samples from suspected metastatic lesions
- Normal Range
- Negative Result: Absence of brown/tan nuclear staining in tissue cells; normal benign prostatic epithelium typically shows strong, diffuse nuclear NKX3.1 staining (positive in normal prostate tissue)
- Positive Result: Presence of brown/tan nuclear staining indicating NKX3.1 expression; typically graded as weak, moderate, or strong based on staining intensity and percentage of positive cells
- Percentage Staining: Reported as percentage of positive cells (0-100%); typically categorized as negative (<5%), focal/weak (5-25%), moderate (25-75%), or diffuse/strong (>75%)
- Staining Pattern: Nuclear localization is the expected pattern; cytoplasmic staining is not considered significant
- Normal prostate tissue shows strong, diffuse nuclear staining; loss or absence of staining may indicate malignancy or abnormal differentiation
- Interpretation
- Strong, Diffuse NKX3.1 Positivity (>75% strong nuclear staining): Consistent with benign prostatic tissue or low-grade adenocarcinoma; supports diagnosis of prostatic origin for malignancy
- Moderate NKX3.1 Staining (25-75%): May indicate intermediate grade adenocarcinoma or mixed benign and malignant tissue; requires correlation with other histologic features and immunomarkers
- Weak or Focal NKX3.1 Staining (5-25%): Suggestive of higher-grade or more aggressive adenocarcinoma with loss of differentiation; associated with worse prognosis
- Negative or Lost NKX3.1 Expression (<5%): Highly suggestive of high-grade invasive adenocarcinoma, loss of prostatic differentiation, or absence of prostatic tissue; indicates aggressive disease with poor prognosis
- Clinical Correlation Required: NKX3.1 results must be interpreted with morphologic findings, Gleason grade/score, PSA levels, and other clinical parameters for complete assessment
- Tissue Quality Considerations: Formalin fixation time, fixative type, antigen retrieval methods, and antibody quality may affect staining results; proper controls must be included for valid interpretation
- Associated Organs
- Primary Organ System: Prostate gland (male reproductive system and urinary system); NKX3.1 is highly specific for prostatic epithelium
- Prostate Cancer (Adenocarcinoma): Loss of NKX3.1 expression is associated with high-grade invasive adenocarcinoma and more aggressive tumors; correlates with Gleason score and clinical progression
- Benign Prostatic Hyperplasia (BPH): Shows strong, diffuse NKX3.1 staining, helping differentiate from malignancy
- Prostatic Intraepithelial Neoplasia (PIN): Atypical lesions may show variable NKX3.1 staining; helps assess risk of malignant transformation
- Metastatic Prostate Cancer: NKX3.1 expression helps confirm prostatic origin of secondary tumors in distant organs (bone, liver, lymph nodes, lungs); lost expression may indicate androgen-independent disease
- Clinical Implications of Abnormal Results: Loss of NKX3.1 indicates aggressive disease with increased risk of metastasis, biochemical recurrence after treatment, and shortened overall survival; may influence treatment decisions and monitoring intensity
- Follow-up Tests
- Additional Immunohistochemistry Markers: PSA (Prostate-Specific Antigen) - confirms prostatic differentiation; P63 or high molecular weight cytokeratin - differentiates benign from malignant tissue; ERG - evaluates TMPRSS2-ERG gene fusion status; Ki-67 - assesses proliferation rate and tumor aggressiveness
- Serum PSA Testing: Baseline and periodic PSA levels to monitor for disease recurrence or progression; PSA velocity and PSA density provide prognostic information
- Molecular Testing: FISH for PTEN deletion, ERG rearrangement; gene expression profiling (Oncotype DX, Prolaris) for risk stratification and treatment planning
- Imaging Studies: MRI of prostate for staging and local extent assessment; CT/bone scan for metastatic disease evaluation if NKX3.1 loss or high-grade cancer found
- Additional Biopsy: May be warranted if initial tissue sampling was limited or diagnosis remains uncertain; repeat biopsy for monitoring known lesions or suspected progression
- Monitoring Frequency: Active surveillance protocols require PSA testing every 3-6 months and periodic imaging; more frequent monitoring recommended if NKX3.1 loss detected; post-treatment follow-up (surgery, radiation, hormone therapy) requires serial PSA monitoring and clinical assessment
- Fasting Required?
- Fasting: Not Applicable
- Reason: NKX3.1 IHC is performed on tissue samples (formalin-fixed, paraffin-embedded), not blood serum; no dietary restrictions apply to specimen collection
- Specimen Collection Preparation: Tissue samples are obtained via prostate biopsy, transurethral resection of prostate (TURP), or surgical prostatectomy; standard biopsy preparation procedures apply
- Pre-Biopsy Instructions (if tissue acquisition via biopsy): Discontinue anticoagulants (warfarin, dabigatran) 3-5 days before procedure; hold aspirin and NSAIDs 1 week prior; discontinue antibiotics or arrange prophylactic antibiotics per institutional protocol; cleanse perineal area the night before; void before procedure; local or regional anesthesia will be used
- Medications: Review anticoagulation status with healthcare provider; may require bridging therapy; continue other routine medications unless specifically instructed otherwise
- Specimen Handling: Tissue must be promptly fixed in 10% neutral buffered formalin for appropriate time (typically 6-24 hours); processing into paraffin blocks follows standard histology protocols; slides must be sectioned at 4-5 micrometers; antigen retrieval is required before IHC staining; internal positive and negative controls must be included with each run
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