Cancer Awareness – Gallbladder Cancer Facts

Approximately 12,000 men and women in the United States are diagnosed with gallbladder cancer annually, leading to an annual estimated 4,000 deaths.1 Gallbladder and other biliary cancers are comparatively rare in the United States, with about 0.7% of new cancer cases classified as gallbladder, contributing approximately 0.6% of cancer deaths yearly.1 Worldwide, gallbladder and other biliary cancers are the twenty-second most frequently diagnosed cancer and the eighteenth leading cause of cancer death, with an annual estimated 219,400 cases and 165,100 deaths.2

Gallbladder carcinoma (GBC) is predominantly found in women (female to male ratio, 3-4: 1), which may be related to increased incidence of gallstones in women.3 In addition to gallstones and gender, there are other risk factors that may influence the development of GBC:4

• Gallbladder polyps: Growths that may form as a result from an embedded gallstone or inflammation.
• Age:
Most patients diagnosed with GBC are in the sixth or seventh decade of life.
• Ethnicity: In the United States, Hispanic and Native Americans have a higher rate of gallbladder cancer than other ethnic groups.
• Smoking: Tobacco use may elevate the risk of death from gallbladder cancer dose-dependently among both men and women.
• Family history: Family history of GBC slightly increases risk of developing GBC.

GBC is a poor prognosis malignancy since it usually presents at a very advanced stage. Early detection of GBC is often difficult because symptoms mimic benign gallbladder diseases, such as gallstones and biliary colic.5 Differentiation of GBC versus non-malignant gallbladder disease is critical to accurate diagnosis and treatment. There have been many immunomarkers reported to be expressed in GBC and not expressed in normal/benign gallbladder: CA 19-9, CEA, Mucin 5AC, S100P, IMP3, GLUT-1, p53, and CDX2.6,7,8,9

As part of our promise of “Fighting Cancer, One Slide at a Time,” Biocare Medical is proud to offer key high-quality immunohistochemistry (IHC) antibodies that aid in accurate classification of gallbladder and other biliary tumors.

Key Antibodies for Gallbladder and Biliary Cancer

Product Name Clone Catalog Number
CA 19-9 BC/121SLE CM 123; PM 123
Carcinoembryonic Antigen (CEA {M}) COL-1 CM 058; PM 058
Mucin 5AC 45M1 CM 231
S100P N/A ACI 3010; API 3010
IMP3 (RM) EP286 ACI 3180; API 3180
GLUT-1 SPM498 CM 408; PM 408
p53 EP9 CME 298; PME 298; IP 298
p53 Tumor Suppressor Protein DO-7 CM 042; PM 042
CDX2 [BC39] BC39 ACI 3184; API 3184; AVI 3184
CDX2 (RM) EP25 ACI 3144; API 3144

Clinical References:

1. Siegel RL, Miller KD, Jemal A. CA Cancer J Clin. 2017 Jan;67(1):7-30.
2. Bray F, et al. CA Cancer J Clin. 2018 Nov;68(6):394-424.
3. Giang TH, et al. Diagn Pathol. 2012 Jan 27;7:10.
4. https://www.cancer.net/cancer-types/gallbladder-cancer/risk-factors
5. https://www.cancer.org/cancer/gallbladder-cancer/detection-diagnosis-staging
6. Hughes NR, Bhathal PS. J Clin Pathol. 2013 Mar;66(3):212-7.
7. Lin F, Chen ZE, Wang HL. Arch Pathol Lab Med. 2015 Jan;139(1):24-38.
8. Xiong L, et al. J Surg Oncol. 2012 Jan;105(1):97-103.
9. Park SY, et al. Oncol Rep. 2009 Sep;22(3):649-57.

Cancer Awareness – Cervical Cancer Facts

Approximately 13,000 women in the United States are diagnosed with cervical cancer annually, leading to an annual estimated 4,000 deaths.1 Cervical cancers are comparatively rare in the United States, with about 0.8% of new cancer cases classified as cervical, contributing approximately 0.7% of cancer deaths yearly.1 Worldwide, cervical cancer is the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death, with an annual estimated 527,600 cases and 265,700 deaths.2

Nearly all cervical cancers are caused by high-risk (oncogenic) human papilloma virus (HPV).3,4 HPV subtypes are broadly classified as high-risk (leading to cervical malignant transformation) or low-risk (leading to benign lesion development).5 The high-risk HPV subtypes, HPV 16 and HPV 18, are the most common subtypes found in cervical tumors. Together, HPV 16 and HPV 18 are the causative agents for greater than 70% of invasive cervical cancers worldwide.5,6 It has been estimated that approximately 10% of the worldwide population have a cervical HPV infection at any given time.7 In spite of this high infection rate, nearly 90% of such infections are naturally cleared by the body within a year or two, and only women with persistent high-risk HPV subtype infections are at risk of progression to cervical cancer.8,9 The slow progression of the disease combined with the availability of screening and HPV vaccination is why many experts consider cervical cancer to be nearly completely preventable.10 Invasive cervical cancer can often be successfully treated if detected at an early stage.

As part of our promise of “Fighting Cancer, One Slide at a Time,” Biocare Medical is proud to offer key high-quality immunohistochemistry (IHC) and in situ hybridization (ISH) reagents that aid in early and accurate classification of cervical tumors and presence of HPV.

Key Antibodies for Cervical Cancer

Product Name Clone Catalog Number
HPV-16* CAMVIR-1 CM 186
HPV Cocktail Broad Spectrum* BPV-1/1H8 + CAMVIR-11 CM 177; PM 177
CA 125 OC125 CM 101; PM 101
Carcinoembryonic Antigen (CEA {M}) COL-1 CM 058; PM 058
p63 4A4 CM 163; PM 163; IP 163; OAI 163; VP 163
CD117/c-kit EP10 CME 296; PME 296; IP 296; OAI 296
MCM2 + TOP2A OT18A11 + UMAB146 API 3181
Topoisomerase II alpha O31 ACI 3045; API 3045
VEGF* EP1176Y CME 356

*Research Use Only (RUO)

Key probes for detecting HPV

Product Name HPV Target Subtype (Classification) Catalog Number
HPV Type 16 Probe (Digoxigenin)** HPV 16 (High-Risk) BRA 4047
HPV Type 18 Probe (Digoxigenin)** HPV 18 (High-Risk) BRA 4048
HPV Type 31 Probe (Digoxigenin)** HPV 31 (High-Risk) BRA 4051
HPV Type 51 Probe (Digoxigenin)** HPV 51 (High-Risk) BRA 4052
HPV Type 6 Probe (Digoxigenin)** HPV 6 (High-Risk) BRA 4045
HPV Type 11 Probe (Digoxigenin) HPV 11 (High-Risk)** BRA 4046

**Analyte Specific Reagents (ASR) for clinical Laboratories to use in developing laboratory developed tests.

Clinical References:

1. Siegel RL, Miller KD, Jemal A. CA Cancer J Clin. 2017 Jan;67(1):7-30.
2. Torre LA, et al. Cancer Epidemiol Biomarkers Prev. 2017 Apr;26(4):444-457.
3. http://www.nccc-online.org/wp-content/uploads/2019/01/10ThingsHPV_CCAM-1.pdf
4. https://www.cdc.gov/cancer/knowledge/publications/fact_sheets.htm
5. de Sanjose S, et al. Lancet Oncol. 2010 Nov;11(11):1048-56.
6. Li N, et al.. Int J Cancer 2011;128:927–35.
7. de Sanjose S, et al. Lancet Infect Dis 2007;7:453–9.
8. Shvetsov YB, et al. Clin Infect Dis 2009;48:536–46.
9. Moscicki AB, et al. Vaccine 2012;30Suppl 5:F24–33.
10. Committee on Adolescent Health Care Immunization Expert Work Group. Obstet Gynecol 2015;126:e38–43.

Cancer Awareness – Early Detection and Tumors of Unknown Origin

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.