Organ Systems, Pulmonary

Lung IHC

Many different markers can be used in neoplastic lung, but the most common involve differentiation between squamous and adenocarcinoma and identifying evidence of neuroendocrine differentiation.

Squamous Versus Adenocarcinoma
Neuroendocrine Differentiation
Napsin A and TTF-1 expression in various tumor types (Bishop, JA, et al).
 
(% +)
(% +)
Lung Tumors
 
 
Adneocarcinoma
79/95 (83%)
69/95 (73%)
  •   Well-differentiated
42/47 (89%)
38/47 (81%)
  •   Mod.-differentiated
27/32 (84%)
24/32 (75%)
  • Poorly-differentiated
11/16 (69%)
7/16 (44%)
  • Squamous Cell Ca.
0/46 (0%)
0/48 (0%)
  • Large Cell Carcinoma
3/9 (33%)
4/9 (44%)
  • Small Cell Carcinoma
0/3 (0%)
1/3 (33%)
Atypical Carcinoid Tumor
0/1 (0%)
1/1 (100%)
Typical Carcinoid Tumor
0/2 (0%)
1/2 (50%)
Non-pulmonary Adenocarcinomas
 
 
Colon Adenocarcinoma
0/5 (0%)
0/5 (0%)
Pancreas Adenocarcinoma
0/31 (0%)
0/31 (0%)
Breast Adenocarcinoma
0/17 (0%)
0/17 (0%)
Mesothelioma (all types)
0/38 (0%)
0/38 (0%)
Renal Cell Carcinomas
 
 
Clear Cell
14/41 (34%)
0/41 (0%)
Papillary
34/43 (79%)
0/43 (0%)
Chromophobe
1/34 (3%)
0/34 (0%)
Thyroid Lesions
 
 
Papillary Carcinoma
2/38 (5%)
37/38 (97%)
Follicular Carcinoma
0/15 (0%)
15/15 (100%)
Follicular Adenoma
0/28 (0%)
28/28 (100%)
CK5

CK5 will stain approximately 70-80% of squamous cell carcinomas with a cytoplasmic staining pattern.  p63 is considered slightly more sensitive, but may give varying positivity in cases of lung adenocarcinoma that can be confusing.  Therefore, CK5 and p63 are often used as part of a panel to diagnose squamous cell carcinoma.  Since p63 is a nuclear marker, these two stains can be performed as a double stain on a single slide with one or two different chromogens.

p63
CK5/6 co-expression with p63 is a sensitive (77%) and specific (96%) marker for squamous cell carcinoma.   p63 appears to be very specific for squamous and urothelial origin.  Only rare other non-squamous cell carcinomas show >50% expression of p63. [Kaufman, O., et. al.]
 
Small cell carcinomas express p63 in approximately 77% of cases (n=14). [Au, NH, et. al.]  This could be a potential pitfall if one is considering a poorly differentiated squamous cell carcinoma and not a poorly differentiated neuroendocrine carcinoma. 
Double Stains

Double stains can be helpful in conserving tissue for small biopsy samples, which is critical to be able to perform testing for ALK, ROS-1, and EGFR mutations.  Nuclear and cytoplasmic markers paired together with different colored chromagens are preferred (e.g. TTF-1/Napsin A for adenocarcinomas and CK5/p63 for squamous cell carcinomas)

Photomicrographs
TTF-1 - Lung Squamous Cell Carcinoma
TTF-1 – Lung Squamous Cell Carcinoma. Benign pneumocytes at the peripheral of the tumor showing TTF-1 expression.
p63-CK5 (double stain) lung squamous cell carcinoma
Co-expression of CK5 (red) and p63 (DAB) in a lung squamous cell carcinoma. Note the diffuse consistent expression of p63.
TTF-1/Napsin A (double stain) - Lung Adenocarcinoma
Napsin A (red) and TTF-1 (DAB) double stain in a lung adenocarcinoma.
References

Bishop, J. A., Sharma, R., & Illei, P. B. (2010). Napsin A and thyroid transcription factor-1 expression in carcinomas of the lung, breast, pancreas, colon, kidney, thyroid, and malignant mesothelioma. Human Pathology, 41(1), 20–25. doi:10.1016/j.humpath.2009.06.014 

Kaufmann, O., et. al. “Value of p63 and CK 5/6 as IHC Markers for the Differential Dx. of Poorly Differentiated and Undifferentiated Carcinomas.” American Journal of Clinical Pathology. 2001;116:823-830
 
Au NHC, Gown AM, Cheang M, et al. P63 expression in lung carcinoma: a tissue microarray study of 408 cases. Appl Immunohistochem Mol Morphol. 2004;12(3):240–247.