The first step in a diagnosis of cancer is the definitive conclusion of the presence of malignant tissue. However, this tissue may not identify the particular form of cancer at work, so further analysis is often necessary. One of the techniques used for this latter diagnosis is immunostaining, where a tissue sample is treated with a reactive dye that becomes activated when it binds to a marker indicative of a certain form of cancer. The binding process then “stains” the tissue—providing a visual indication of the marker’s presence and, therefore, a determination of the type of cancer at hand.

One of the most difficult differentials to make is between malignant mesothelioma and poorly differentiated forms of adenocarcinoma of the lung and squamous cell carcinoma of the lung. Morphology analysis of the fluid from an effusion is not able to differentiate between these cancers, so scientists are searching for protein markers that can differentiate between them. Researchers from the University of Michigan School of Medicine have recently released a study that identifies possible markers.

Introduction to the Study

The search for biomarkers for mesothelioma and other cancers is an especially active form of research. The need for accurate differential diagnoses has driven researchers to experiment with a number of substances as possible markers, such as calretinin, CEA, BerEP4, CD15 and cytokeratins, but many of these do not have the high specificity required for such important decision-making. Some recent studies have recently identified a few more substances as possible makers—WE-1, p63, MOC31 and mesothelin—and it is these agents that the authors of the present study looked at. They also looked at the ability of cytokeratin staining to differentiate between the cancers.

The authors studied 43 samples of malignant effusions. 10 were adenocarcinoma (ADC), 15 were squamous cell carcinoma (SCC) and 18 were malignant mesothelioma, mainly pleural mesothelioma. Immunostaining for each of the four markers identified above (WE-1, p63, MOC31 and mesothelin) was performed on each sample.

WT-1

The authors found that WT-1 was perfect for determining a malignant mesothelioma diagnosis, as it stained in 100% of the mesothelioma cases and none of the ADC or SCC cases. Calretinin had previously been identified as the best positive marker for differentiating mesothelioma, but the authors recommended further study and greater use of WT-1 because of their excellent results.

P63

Antibody-staining against P63 showed significant staining for SCC, a lower threshold for ADC and none for mesothelioma. The authors support using a combination of P63-negative status and WT-1-positive status to differentiate mesothelioma from both SCC and ADC.

MOC31

The authors conclude that MOC31 wasn’t an effective marker by itself. It stained for ADC 100% of the time, 67% of the time for SCC and 35% for mesothelioma, so it could not differentiate between the malignancies enough on its own. However, when used in a panel with other antibody staining, the authors felt it could be used to differentiate between ADC/SCC and mesothelioma.

Mesothelin

Mesothelin is a marker that is under active investigation, but there are conflicting results returned from different studies regarding its efficacy. Some studies have come back with a 100% success rating for determining a mesothelioma diagnosis, but the authors of this study expressed disappointment at the results they obtained when staining for it. Their figures returned the following results: 100% ADC and 60% SCC, but only a figure of 47% for mesothelioma. The authors do not recommend mesothelin because of these results.

Cytokeratin Staining

The results for K903 and CK5/6 showed that ADC and SCC can be differentiated using cytokeratin staining, but it is only recommended if mesothelioma has been conclusively ruled out before the investigation.

Conclusion

The identification of new markers in cancer diagnosis is an important advancement on our knowledge. Early identification allows the patient to receive earlier treatment, which can be greatly beneficial. With a malignancy such as malignant mesothelioma, which has generally resisted long term treatment, early diagnosis is essential to maximizing patient response.

Labels: LungCancer, mesothelioma