Immunostaining of lung cancer cells highlighting key protein markers.

Lung Cancer Diagnosis: Can a Simple Stain Save Lives?

Mira Elwood in Health & Wellness August 2025 • 4 min read.

"New research highlights how immunostaining for key proteins can drastically improve the accuracy of lung cancer diagnosis, leading to better treatment decisions."

Lung cancer is a leading cause of cancer deaths worldwide. Accurately distinguishing between squamous cell carcinoma and non-squamous cell carcinoma is crucial because treatment options differ significantly. For instance, certain drugs like bevacizumab are contraindicated for squamous cell carcinoma due to the risk of bleeding, while pemetrexed is primarily effective against non-squamous types.

However, getting a precise diagnosis can be challenging when only a limited number of tumor cells are available from biopsies or cytology smears. Traditional methods often fall short, leading to the need for more reliable diagnostic tools.

A recent study investigated the use of immunostaining—a technique that uses antibodies to detect specific proteins in cells—to improve the accuracy of lung cancer diagnosis. By examining various combinations of antibodies, researchers aimed to identify the optimal method for differentiating between squamous and non-squamous cell carcinoma.

Decoding the Protein Markers: How Immunostaining Works

Immunostaining of lung cancer cells highlighting key protein markers.

The study focused on several key proteins: thyroid transcription factor 1 (TTF-1), Napsin A, p40, and cytokeratin 5 (CK5). TTF-1 and Napsin A are typically found in non-squamous cell carcinomas (adenocarcinomas), while p40 and CK5 are more characteristic of squamous cell carcinomas. By staining tumor samples with antibodies that target these proteins, pathologists can determine the type of lung cancer present.

Researchers analyzed tumor imprint smears from 70 lung carcinoma cases, scoring the results based on the area and intensity of positive staining. TTF-1, Napsin A, and CK CAM5.2 (another marker for adenocarcinoma) were assigned positive values, while p40, CK5/6, and CK5 were assigned negative values. This scoring system allowed for objective evaluation and comparison of different antibody combinations.

TTF-1: 88% sensitivity in adenocarcinoma
Napsin A: 85% sensitivity in adenocarcinoma
CAM5.2: 100% sensitivity in adenocarcinoma
p40: 90% sensitivity in squamous cell carcinoma
CK5: 86% sensitivity in squamous cell carcinoma
CK5/6: 76% sensitivity in squamous cell carcinoma

The most effective combination was TTF-1, Napsin A, p40, and CK5, which accurately differentiated between adenocarcinomas and squamous cell carcinomas. Using this combination, all adenocarcinomas scored >1, and all squamous cell carcinomas scored <-2.

The Future of Lung Cancer Diagnostics

This study demonstrates the potential of immunostaining as a valuable tool in the differential diagnosis of lung cancer, especially when dealing with limited tumor samples. By using a combination of TTF-1, Napsin A, p40, and CK5, pathologists can improve the accuracy of their diagnoses and guide treatment decisions more effectively.

While the study's findings are promising, the researchers acknowledge that this method may not be able to differentiate all cases. Further investigation of new markers and refinement of the scoring system are needed to improve diagnostic accuracy even further. Specifically, incorporating mucin 5B for mucinous adenocarcinomas and identifying specific markers for large cell carcinoma are potential areas for future research.

Ultimately, the goal is to create a diagnostic index that can be used to aid in the diagnosis of lung cancer, ensuring that patients receive the most appropriate and effective treatment based on the specific type of cancer they have.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.3892/ol.2015.3045, Alternate LINK

Title: Immunostaining For Thyroid Transcription Factor 1, Napsin A, P40, And Cytokeratin 5 Aids In Differential Diagnosis Of Non-Small Cell Lung Carcinoma

Subject: Cancer Research

Journal: Oncology Letters

Publisher: Spandidos Publications

Authors: Satoshi Ikeda, Keishi Naruse, Chigusa Nagata, Masami Kuramochi, Takuya Onuki, Masaharu Inagaki, Keiko Suzuki

Published: 2015-01-01

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Everything You Need To Know

1

What is immunostaining and how is it used in lung cancer diagnosis?

Immunostaining is a technique that uses antibodies to detect specific proteins in cells. In the context of lung cancer diagnosis, it helps differentiate between squamous cell carcinoma and non-squamous cell carcinoma. This is important because these two types of lung cancer require different treatments. By identifying specific protein markers like thyroid transcription factor 1 (TTF-1), Napsin A, p40, and cytokeratin 5 (CK5) using immunostaining, pathologists can make more accurate diagnoses, leading to better patient outcomes.

2

What are the key proteins used in immunostaining, and what do they indicate?

The key proteins investigated were thyroid transcription factor 1 (TTF-1), Napsin A, p40, and cytokeratin 5 (CK5). TTF-1 and Napsin A are typically found in non-squamous cell carcinomas, particularly adenocarcinomas. p40 and CK5 are more characteristic of squamous cell carcinomas. The presence or absence of these proteins, as revealed by immunostaining, helps pathologists classify the type of lung cancer. For instance, TTF-1 showed 88% sensitivity in adenocarcinoma, while p40 had 90% sensitivity in squamous cell carcinoma. The combination of these markers improves diagnostic accuracy.

3

Why is accurate diagnosis of lung cancer so important?

The primary implication of accurate lung cancer diagnosis is the ability to tailor treatment strategies. For example, bevacizumab is contraindicated for squamous cell carcinoma due to the risk of bleeding, but pemetrexed is primarily effective against non-squamous types. Precise identification of the cancer type using immunostaining allows oncologists to select the most appropriate and effective therapies, improving treatment outcomes and reducing potential side effects.

4

How does immunostaining help when only limited tumor samples are available?

If only a limited number of tumor cells are available from biopsies or cytology smears, it becomes challenging to get a precise diagnosis using traditional methods. Immunostaining provides a solution by allowing pathologists to analyze the available cells and identify specific protein markers. The study showed that by using a combination of TTF-1, Napsin A, p40, and CK5, accurate differentiation between adenocarcinoma and squamous cell carcinoma is possible, even with limited samples.

5

Which combination of protein markers proved most effective in distinguishing between lung cancer types?

The study found that the most effective combination for differentiating between adenocarcinomas and squamous cell carcinomas was TTF-1, Napsin A, p40, and CK5. This combination allowed researchers to accurately classify the cancer type based on the presence or absence of these protein markers. This scoring system allowed for objective evaluation and comparison of different antibody combinations. The combination of these markers increases diagnostic accuracy and guides treatment decisions.