The main idea is the exact name behind the acronym ALK. It stands for Anaplastic lymphoma kinase, a receptor tyrosine kinase that was first described in association with anaplastic large cell lymphoma. In NSCLC, rearrangements involving this gene produce a constantly active kinase that helps drive cancer growth, which is why ALK inhibitors are an important targeted therapy. The other possible expansions don’t match the established gene name—leukemia, lymphoid, or adenosine kinase refer to different proteins or contexts.

Immunohistochemical profiling for hepatocellular carcinoma relies on recognizing hepatocytic differentiation and the distinctive vascular pattern these tumors often show. HepPar1 is a classic marker of hepatocyte lineage, so its positivity points toward hepatocytic origin. Glypican-3 (GPC3) is more specific for HCC and helps distinguish it from benign liver lesions and many other tumors. Alpha-fetoprotein (AFP) staining supports hepatocellular differentiation when present, even though not all HCCs express it; its presence adds diagnostic weight. CAM5.2 detects low molecular weight cytokeratins (CK8/18), reflecting epithelial characteristics of hepatocytes and aiding separation from non-hepatocytic biliary tumors. CD34 highlights the sinusoidal capillarization pattern seen in HCC, a vascular feature that contrasts with the vascular patterns of metastases or cholangiocarcinoma. Taken together, this combination of markers builds a coherent immunoprofile for primary hepatocellular carcinoma, increasing diagnostic confidence more than any single marker alone. The other marker sets focus more on cholangiocarcinoma, pancreaticobiliary, or lung origins and are less supportive of a hepatocellular diagnosis.

In immunohistochemistry, the goal is to detect specific proteins in tissue to help classify the tumor and its origin. WT1 is a classic marker that supports serous ovarian carcinoma, and HER2 can be evaluated in some ovarian cancers for targeted therapy considerations. CA-125 is tied to ovarian cancer as a serum marker and can be detected in tissue in some settings, though its primary role is not as an IHC workhorse. BRCA1, by contrast, is a gene whose status is determined by genetic/molecular testing (sequencing, deletion/duplication analysis) rather than an immunohistochemical stain. It informs hereditary risk and PARP-inhibitor therapy, not the routine histologic panel used to identify ovarian carcinoma. So BRCA1 is not included in the IHC panel.

Endocervical adenocarcinoma is strongly linked to high‑risk HPV infections, with certain genotypes more commonly found in glandular cervical cancers. HPV 18 is particularly associated with adenocarcinomas, and HPV 45 also frequently appears in glandular lesions. HPV 16 is the most common genotype in cervical cancers overall and is seen frequently as well, contributing to endocervical adenocarcinomas alongside 18 and 45. By contrast, HPV 31 is more often tied to squamous lesions than to glandular cancers. So a trio that includes 16, 18, and 45 best reflects the genotypes commonly associated with endocervical adenocarcinoma.