Biocare Medical takes great pride in our promise of “Fighting Cancer, One Slide at a Time.” Our focus in the fight against cancer is realized through our high-quality immunohistochemistry (IHC) and in situ hybridization (ISH) reagents and instrumentation. Specifically, our sensitive and specific antibodies, molecular probes, and detection chemistries support early and accurate classification of many cancer types, including tumors of unknown origin. Early detection of cancer significantly increases the chances for successful treatment and can effectively reduce the associated mortality, while accurate diagnosis of tumors of unknown origin allows for determination of the best treatment option.

Early Diagnosis

Early diagnosis for the nine most common cancers (bladder, colon, breast, cervical, ovarian, malignant melanoma, lung, prostate, and testicular cancers), significantly increased survival rates1. When the cancer was diagnosed at stage one or two, 80% of patients survived for at least 10 years.

The appropriate immunohistochemical panels, as well as ISH and other molecular testing, are a critical component in the systematic algorithm of specific, accurate diagnosis2. In the past decade, the clinical diagnostic precision of organ- and tumor-specific immunomarkers, along with the clinical validation of effective IHC panels, has improved significantly.

Tumor of Unknown Origin

When the lineage of a tumor can be identified through standard morphological means, organ- or tumor-specific immunomarkers would be utilized to determine an accurate diagnosis. If the tumor lineage cannot be easily identified via morphological analysis, IHC plays a critical role in the determination of the site of primary origin2,3. Often, the first diagnostic IHC panel will include antibodies directed against lymphoid antigens (Leukocyte Common Antigen [LCA] Cocktail), epithelial antigens (Pan Cytokeratin [AE1/AE3]), melanocytic antigens (S100 protein, SOX10), and sarcoma antigens (Muscle Specific Actin).

Mainline Screening Immunomarkers for Tumors of Unknown Origin

Lymphoma Carcinoma Melanoma Sarcoma
Leukocyte Common Antigen (LCA) Cocktail Pan Cytokeratin [AE1/AE3] S100 Protein Cocktail/SOX10 Muscle Specific Actin

For each of the mainline screening immunomarkers in the table above, once a positive categorical origin is confirmed (lymphoma, carcinoma, melanoma, or sarcoma), additional markers will be tested to determine organ-specific origin of the primary tumor2-4.

Secondary Screening Panels for Tumors of Unknown Origin

Lymphoma Carcinoma Melanoma Sarcoma
CD20 [L26] Cytokeratin LMW (8/18) HMB45 Smooth Muscle Actin
PAX-5 p63 + CK5 / Desmoglein 3 + p40 (M) Tyrosinase Desmin
CD3 [LN10] Cytokeratin 7 / Cytokeratin 19 MART-1 Cocktail Myogenin
CD15 Cocktail / CD30 (Ki-1) CDX2 (M) + CDH17 (RM) / Cytokeratin 20 Pan Melanoma Cocktail-2 CD31
ALK [5A4] TTF-1 + Napsin A (RM) Microphthalmia Transcription Factor (MiTF) CD34
Kappa (M) + Lambda (P) Estrogen Receptor (ER) [SP1]* / Progesterone Receptor (PR) [16]* N/A CD99
CD68 / CD163 c-erbB-2/HER2 N/A ERG
CD10 Prostein + PSA + NKX3.1 / ERG N/A N/A
Cyclin D1 Synaptophysin N/A N/A
CD4 + CD8 PAX8 (M) N/A N/A
Bcl-2 / Bcl-6 [LN22] SALL4 N/A N/A
CD7 CD56 / MASH1 N/A N/A
Terminal Deoxynucleotidyl Transferase Hepatocyte Specific Antigen / Arginase-1 N/A N/A
MUM-1 / CD138 Glypican-3 (GPC3) N/A N/A
N/A GATA-3 + Uroplakin II N/A N/A

*These products are Research Use Only, not FDA cleared for clinical diagnosis.

Clinical References:

1. Wise J. BMJ. 2016 Jun 12; 353:i3277.
2. Selves J, et al. Cancers. 2018; 10(4):108.
3. Kandukuri SR, et al. Arch Pathol Lab Med. 2017 Aug; 141(8):1014-1032.
4. Chu P, Wu E, Weiss LM. Mod Pathol. 2000 Sep;13(9):962-72.

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