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Proteomics study for deciphering Pituitary adenoma pathology
Introduction
Pituitary adenomas are tumor of endocrine gland that result when the anterior pituitary gland is
afflicted by a tumor and considered as third most common brain tumor.Pituitary tumors account
for 10% of all primary brain tumors, making them the third most common primary brain tumors
in adults following meningioma and gliomas. The epidemiological studies over the past few
decades have shown that the estimated prevalence rate of pituitary adenomas is 10-20 per million
with an incidence of 3-4 new cases per year. Although pituitary tumors cause considerable
morbidity and mortality due to their hormonal and space occupying effects, they are rarely
metastatic. So, pituitary tumor cells serve as an important model of dysregulated cell
proliferation.It is a chronic disease associated with significant morbidity affecting multiple organ
systems. Tumors are classified on the basis of size and functionality (Ezzat et al., 2004). The
symptoms are due to burden due to mass of tumor on such as headache, vision loss, hearing loss
and symptoms also produced due to functioning adenomas which produce hormones or it can be
non-functioning. For example, in acromegaly the most common symptoms involve abnormal
growth of the hands, face and feet.Radiology histology and endocrinology profile is used as
diagnostic tool but due to smaller size and non functionality of adenomas theses method fails to
detect the adenoma in early stage until it present some symptoms (Calligaris et al., 2015).The
past two decades have shown significant advancements in the knowledge and treatment of
pituitary
adenomas.
Therapeutic
approaches
presently
used
are
surgery
(Transsphenoidaladenomectomy), or radiotherapy/ radiosurgery, drugs (Grasso et al., 2012). At
present the most promising treatment is surgery. The surgical resection of these tumors can be
highly effective in a few cases but it often fails to cure those with invasive or recurrent
tumors.These difficulties underscore the need for improved predictive biomarkers for early
detection of the disease and the development of mechanisms for targeted medical therapies.
Role of Mutations
Various studies were done for better understanding of disease pathology that’s help in finding
outthe better diagnostic and prognostic markers. Pituitary adenomas generally result due to the
clonal expansion of a single mutated cell. Molecular studies have identified a number of genetic
and epigenetic abnormalities that may have a possible role in pituitary tumorigenesis. Mutations
in multiple oncogenes and tumor suppressor genes have been associated with pituitary
tumorigenesis. The well studied molecules include gsp, PTTG, and MEG3. In contrast, very few
germline mutations have been associated with pituitary adenomas. A dominant mutation occurs
in the Gsα gene in about 30% of somatotropinomas, but this mutation is rare in other pituitary
tumors. The available data suggests that besides these mutations, the pathogenesis of pituitary
adenoma also depends on a variety of other gene mutations such as AIP, CDKN1B, CDKN2A,
CDKN2C, BMP4, Cyclin D1, p53, GADD45G, RAS and Rb hence these mutations can change
the expression profile of the these various genes (Osamura et al., 2008) .
Role of differential expression of proteins
MALDI ISD MS is used to diagnosed as well as molecular characterization of non pathology
pituitary sample and found that the differential expression of protein level as compared to normal
pituitary gland. Over expressed proteins can be used as biomarker for detection of disease as well
as different protein content can differentiate the functionality of adenoma on the basis of
hormone secretion. The abnormal pattern of hormonal secretion can alter signaling pathway
hence the expression and characterization of pituitary adenoma will altered (Calligaris et al.,
2015). Mass spectrometry technique is also used to differentiate functional as well as non
functional pituitary adenomas on the basis of differential expression of protein in both type of
adenoma and also demonstrate the invasive and non invasive category of different type of
adenoma in different patients. The outcome of surgery is enhancing if the invasiveness of tumor
is known because it will help for better surgery as well as to reduce the post surgery
complications. The differentials expressions of the protein such as down regulation and
upregulation disclose the phenomena of alter signaling pathway that involved in disease
pathology. The alter signal can help in finding out new therapeutic techniques for treatment of
different type of pituitary adenoma (Zhan et al., 2014).
Conclusion
Molecular characterization of pituitary adenomas at proteomic level with advance technology
will help in identification of novel early detection secretory or non secretory biomarkers. It will
also lead to the understanding disease pathology and signaling mechanism which may be
involved in tumorigenesis. This in turn will be helpful in developing targeted medical therapies.
References
1. Ezzat S, Asa SL, Couldwell WT, Barr CE, Dodge WE, Vance ML, McCutcheon IE. The
prevalence of pituitary adenomas. Cancer. 2004 Aug 1;101(3):613-9.
2. Calligaris D, Feldman DR, Norton I, Olubiyi O, Changelian AN, Machaidze R, Vestal
ML, Laws ER, Dunn IF, Santagata S, Agar NY. MALDI mass spectrometry imaging
analysis of pituitary adenomas for near-real-time tumor delineation. Proceedings of the
National Academy of Sciences. 2015 Aug 11;112(32):9978-83.
3. Grasso LF, Pivonello R, Colao A. Somatostatin analogs as a first-line treatment in
acromegaly: when is it appropriate?. Current Opinion in Endocrinology, Diabetes and
Obesity. 2012 Aug 1;19(4):288-94.
4. Osamura RY, Kajiya H, Takei M, Egashira N, Tobita M, Takekoshi S, Teramoto A.
Pathology of the human pituitary adenomas. Histochemistry and cell biology. 2008 Sep
1;130(3):495-507.
5. Zhan X, Desiderio DM, Wang X, Zhan X, Guo T, Li M, Peng F, Chen X, Yang H, Zhang
P, Li X. Identification of the proteomic variations of invasive relative to non‐invasive
non‐functional pituitary adenomas. Electrophoresis. 2014 Aug 1;35(15):2184-94.
Plagiarism Check;
1. model of dysregulated cell proliferation.It is a chronic- Plagiarized
2. Molecular studies have identified a number of genetic and- Plagiarized
3. pattern of hormonal secretion can alter signaling pathway- Plagiarized