The Diagnostic Value of P53 and Desmin in the Differentiation between Reactive Mesothelial Cells and Metastatic Adenocarcinoma in Pleural Effusion

Mesothelial cells are specific cells in serous cavities; when serous membranes stayed on process of inflammation or long time in effusion, these cells change in nucleus and cytoplasm feature. In some cases, morphological differentiation between reactive mesothelial cells and adenocarcinoma in serous effusions is extremely difficult [1]. One the other hand some serotypes have a malignant origin and determining the etiology of making effective therapeutic interventions and finding malignancy is more important. It is very difficult to differentiate between metastatic and reactive adenocarcinoma pleural effusions in serous fluids. A Received: May 10, 2019


Introduction
Mesothelial cells are specific cells in serous cavities; when serous membranes stayed on process of inflammation or long time in effusion, these cells change in nucleus and cytoplasm feature. In some cases, morphological differentiation between reactive mesothelial cells and adenocarcinoma in serous effusions is extremely difficult [1]. One the other hand some serotypes have a malignant origin and determining the etiology of making effective therapeutic interventions and finding malignancy is more important. It is very difficult to differentiate between metastatic and reactive adenocarcinoma pleural effusions in serous fluids. A cytological examination of serum fluids is performed to diagnose the cancers involved in the peritoneum or pericardial spaces.
About 75% of the malignant tumors are in the pleural metastasis of carcinomas [2,3]. A malignant pleural fluid is the first to see the presence of cancer in 46% of patients. The most common malignancies, such as pulmonary, breast, and gastrointestinal tumors, are the most common metastasis to serous fluids, which are more common in adenocarcinoma.
Metastatic carcinoma cells can have a wide variety in shape, which leads to difficult differentiation between mesothelial cell and adenocarcinoma cells in some cases. Often, when reactive cells are mixed with tumor cells in a cytological sample, the use of immunohistochemistry markers can help to differentiate them [4]. In order to avoid false diagnosis, the interpretation of immunohistochemical responses can help differentiate them and interpret the immunohistochemical response in each cell based on conventional cytology analysis. Immunocytochemistry can be done in samples such as flow cytometry [5]. Although, the differentiation is based on the usual morphological findings and history of the patient in terms of the presence or absence underlying malignancy [6]. In 15% of cases, the differentiation of mesothelial reactive cells from adenocarcinoma is not possible based on simple morphology.
On the other hand, the person may not mention a history of primary malignancy and the positive posture is the first manifestation of adenocarcinoma. TP53 is one of the most frequently mutated genes in human cancers.
The most common mutations are single base substitutions that alter protein function. Some of the mutations being oncogenic confer gain-of-function properties [7]. Somatic mutations at specific residues have been associated with specific clinical phenotypes in different type of cancer. In addition to being frequently mutated in cancers, the gene is also highly polymorphic. The fact that some germline variants in the gene may modulate the individual susceptibility to develop cancer has evinced particular interest for the potential use as predictive markers [8]. In recent studies, immunoreactive antibodies against mesothelial cells have been introduced, which show no reaction with carcinoma cells. Recommended mesothelial markers include Calretinin, thrombomodulin, cytokeratin5/6, and HBME1 [9][10][11][12][13][14][15][16]. Therefore, the aim of this study is using immunohistochemistry to distinguish reactive mesothelial cells from metastatic adenocarcinoma in pleural effusions.

Methods and Materials
This cross-sectional descriptive-analytic study will be carried out in the cytology department of Al-Zahra Hospital. The population studied is women and men over the age of 40 who are under the tap due to their presence in the pleura area (Approval code:395975).

Results
The present study was performed on 64 patients with pleural     types of tumors are sarcoma, breast cancer, leukemia, brain tumors, and adrenocortical carcinoma. The TP53 gene mutation has been identified in 50-70% of patients with lung cancer [4].
This study based on molecular methods. In the current study, immunohistochemically detectable p53 was seen in all malignant pleural adenocarcinomas and in few of the reactive hyperplasias.
Strongly positive staining of p53 in reactive mesothelial cells was zero and in metastatic adenocarcinoma, it was 68.8 %Weakly positive staining of p53 in reactive mesothelial cells was 3.1% and in metastatic adenocarcinoma, it was 31.3%.
In a study p53 immunostaining showed nuclear positivity in 31 out of 41 malignant effusions (75.6%) and for the cases that showed p53 immunostaining only, 9 out of 10 cases (90%) were malignant [5]. Several studies have suggested that p53 immunostaining does not occur in benign mesothelium but is more common in malignant cells involving serous effusions [6][7][8][9]. In a study to differentiate between malignant and benign effusions, p53 immunocytochemical staining had been advocated as a malignant marker in 91 pleural and peritoneal serous effusions. p53 was significantly more expressed in malignant than benign effusions (p < 0.0001). p53 positivity rate was found in 75.6% malignant effusions true positive and in 6% of benign effusions [10]. In another study, mutations in TP53 were reported in patients with head and neck tuberculosis of 60%, which is consistent with the present study due to the positive TP53. In this study, all of the tumor's participants were TP53 positive, which means the TP53 correctly detects all cancer patients [11]. carcinomas specimens [12].

Conclusion
It is very important to differentiate between metastatic adenocarcinoma and reactive mesothelial cells in pleural effusions especially overlapping cases which differentiation is critical. The staining with Desmin and p53 are useful in differentiating reactive mesothelial cells from metastatic adenocarcinoma in pleural effusion.