p16 is a tumor suppressor protein that is a cyclin-dependent kinase inhibitor and is essential in regulating the cell cycle. p16 overexpression is a surrogate biomarker of HPV infection (high-risk HPV types), which makes it useful in evaluating HPV-associated squamous and glandular neoplasia of the lower gynecologic trac.

Why P16:

• Infection by the human papilloma virus (HPV) is the most common sexually transmitted agent, and 80% of sexually
  active women will have had HPV in their lifetime. HPV high-risk types 16 & 18 cause 70% of cervical cancer cases.
• Human papilloma virus can be detected in 99.7% of women with histologically confirmed cervical cancer, affecting
  some 500,000 women per year.
  Cervical cancer is one of the few cancers that can be easily diagnosed in its early and well-described premalignant
  stages. Since the malignant progression of HPV infected lesions takes years or even decades after HPV infection,
  early HPV detection could completely prevent cervical carcinoma development.

BOB.1 antibody is a B-lymphocyte transcriptional coactivator that specifically associates with either OCT1 or
OCT2. It boosts the OCT1 mediated promoter activity and to a lesser extent, that of OCT2. It has no intrinsic DNA
binding activity. BOB.1 and Oct-2 are useful for the B-lineage determination of CD20-plasmablattic or primary
effusion subtypes of diffuse large B-cell lymphoma (DLBCL). It recognizes the POU domains of OCT1 and OCT2. It
is essential for the response of B-cells to antigens and required for the formation of germinal centers.

Why BOB.1:

• To indentify B cells in germinal centers, mantle cells and lymphomas
• Determine lineage of CD20 negative B cell neoplasms
• Help differentiate classical Hodgkin's lymphoma (BOB1 negative) from primary mediastinal large B-cell
  lymphoma

Sal-like protein 4 (SALL4) is a zinc-finger transcription factor that serves as a master regulator of embryonic
pluripotency and is involved in processes associated with stem cell activities. SALL4 expression in germ cells
makes it a useful marker for germ cell tumors such as seminoma, embryonal carcinoma, yolk sac tumors and
teratomas. SALL4 expression is also seen in the spermatogonia of normal testis.

Why SALL4:

• General marker of germ cell tumors (SALL4+) and differentiation from sex cord stromal tumors (SALL4+)
• Distinguishes ovarian yolk sac tumor (SALL4+) from clear cell carcinoma (SALL4+)
• Marker of stem cell-like dedifferentiation in many non germ cell cancers
• Sensative (~100%) marker for extragonadal yolk sac tumor with strong diffuse staining
• Rhabdoid tumor (SALL4+) versus epithelioid sarcoma (SALL4+)

Villin is one of the gelsolin family of calcium regulated actin binding proteins. Normally expressed in the brush
border of epithelial cells lining the gastrointestinal tract, hepatobiliary tract and renal proximal convoluted
tubules. in colorectal carcinoma, Villin is highly expressed. In practice, Villin can be included in the panel used
for metastatic carcinoma to detect colorectal origin.

Why VILLIN:

• Important marker for confirming the site of origin of
  metastatic carcinoma
• Loss of villin immunostaining of colorectal carcinoma
  is associated with poor differentiation and survival villin
  positive in varing percentage:
  - Colorectal carcinoma (82 - 84.9%)
  - Gastrointestinal neuroendocrine tumore (72%)
  - Endocervical adenocarcinoma (93.3%)