
<b>Autoimmune phenomena are involved with LMS in two ways...

1. As a causative agent, causing cancer. </b> 
Autoimmune diseases often have antibodies against the patient's DNA... anti-DNA antibodies...  which can predispose toward DNA damage, and if against the p53 gene, can disable the guardian of the genome... so that mutations can accumulate.

<b>2. Paraneoplastic syndromes.  The cancer causes autoimmune phenomena.    </b>
These are collections of things that happen when people have cancer.  My gluten enteropathy [an autoimmune problem] surfaced then, AFTER the cancer.  Often a vasculitis [also an autoimmune problem] can occur after a cancer is diagnosed.

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<b>Malignancy in Autoimmune Diseases</b>

Association between antecedent autoimmune diseases and malignancy, ... has been reported in generalized autoimmune diseases such as systemic lupus erythematosus, dermatomyositis, and rheumatoid arthritis, as well as in organ-specific autoimmune diseases such as Sjogren's syndrome and chronic thyroiditis.
..The activation of rheumatoid factor genes such as Humkv 325 and Vg was considered as one of the triggering factors to advance lympho-proliferative disorders (LPD), from the benign to malignant state. 

A high amount of the bcl-2 protein expression was detected ...in patients with SS, suggesting that the activation of this gene plays an important role in the progression of the lesion from benign to malignant...
Accumulation of many genetic abnormalities including bcl-2 and p53 genes by chronic stimulation of T and B cells at the site of the autoimmune reaction may be important in the high occurrence of LPD in patients with autoimmune diseases.
&&url PMID: 8681020 


<b>p53 Autoantibodies in Patients with Autoimmune Disease</b>

With few exceptions, autoantibodies directed against the gene product of the tumor suppressor gene p53 are only detected in cancer patients. 

From 73 patients with various autoimmune diseases, we obtained 17 sera with elevated autoantibodies against the p53 protein comprising patients with SLE, Graves'disease, and immune vasculitis ...  The overall prevalence (23%) of p53 autoantibodies was comparable to that in various cancers; 

Patients with autoimmune diseases face an increased risk for malignancies. .
&&url PMID: 10789988 


<b>p53 Antibodies in the sera of patients with various types of cancer</b>

.. 130 papers published ... demonstrate that p53 antibodies (p53-Abs) are found predominantly in human cancer patients with a specificity of 96%. ...
It has been demonstrated that this immune response is due to a self-immunization process linked to the strong immunogenicity of the p53 protein. The clinical value of these antibodies remains subject to debate, but consistent results have been observed in breast, colon, oral, and gastric cancers, in which they have been associated with high-grade tumors and poor survival. 
The finding of p53 Antibodies in the sera of individuals who are at high risk of cancer, such as exposed workers
or heavy smokers, indicates that they have promising potential in the early detection of cancer.
&&url PMID: 10766157


Antinuclear antibodies (ANAs) reactive with a limited spectrum of nuclear antigens are characteristic of systemic lupus erythematosus (SLE) and other collagen vascular diseases, ......  our results imply that autoimmunity can be initiated by a "hit and run" mechanism in which the binding of a viral antigen to a self protein triggers an immune response that subsequently can be perpetuated by self antigen.
&&url PMID: 8145041 


<b>Sarcoma and thyroid disorders</b>

We have recently observed that many of our sarcoma patients presented also with thyroid disorders. Literature data are almost unavailable on this topic. 

..analysis of files of patients with sarcoma and clinically overt thyroid disorders was carried out... 28 patients (4.6%) had an associated significant thyroid disorder.

 The types of sarcoma were mainly liposarcoma followed by malignant fibrous histiocytoma, leiomyosarcoma and bone sarcoma. ... The interval between the diagnosis of the thyroid disorder and the sarcoma varied between -14 years (thyroid first) and +16.5 years (thyroid later) with a median of -0.2 years. Thyroid disorders included goiter, thyroiditis and carcinoma. There are both basic-science and clinical evidence to a possible common pathway that leads to the association between overt thyroid disorders and sarcomas of bone or soft tissues. Oncogene erbA activity is related to thyroid receptors to T3 and to development of sarcoma. .... The possible clinical implications are the need to screen patients with sarcoma to thyroid disorders, and patients with thyroid disorders for malignant diseases.
&&url PMID: 12066223  


<b>Autoantibodies to p53 in sera of patients with autoimmune thyroid disease.</b>

Mutations in the tumor suppressor gene, p53, lead to intracellular accumulation of abnormal p53 protein and are associated with p53 autoantibodies. p53 also accumulates in autoimmune diseases and Hashimoto's thyroiditis, but it is unknown if p53 autoantibodies occur in the latter. 

We measured p53 autoantibodies in the sera of 93 patients with thyroid disease and 19 patients without thyroid disease. Anti-p53 antibodies were detected in the sera from 4.2% (2/48) of patients with autoimmune thyroid disease, including one patient with Hashimoto's thyroiditis (3.7%, 1/27) and one with Graves' disease (4.8%, 1/21).
A third patient with pseudohypoparathyroidism, but without thyroid disease, was also positive (1/19; 5.2%). 

None of 19 patients with differentiated thyroid cancer had anti-p53 antibodies. 

We conclude that anti-p53 antibodies can be detected in the sera from approximately 4% of patients with autoimmune thyroid
disease. This finding suggests that increased DNA damage and apoptosis may be associated with autoimmune thyroid disease.
&&url PMID: 10807162 


<b>Programmed cell death (apoptosis)</b>

Programmed cell death is a physiological, energy-consuming mechanism leading to suicide of the cell. Cell death is accomplished by the activation of endonucleases that fragment the cell's nuclear DNA. Some tumour cells remain susceptible to programmed death. These are hormone- and growth factor-dependent tumour cells. Hormone or growth factor deprivation induces signals leading to apoptosis. Other tumours gain strong resistance to apoptosis. ...

Loss of antioncogene p53 provides for resistance against programmed cell death.
Breakdown of resistance to apoptosis in tumour cells can be achieved by oncolytic viruses; generation of lymphotoxin and tumour necrosis factor; monoclonal antibodies; transfection with plasmid vectors carrying p53; gamma irradiation; and certain chemotherapeutic agents.
&&url PMID: 1817429 


<b>autoimmune features in patients with malignancies.</b>

Patients with malignant diseases may develop autoimmune phenomena and rheumatic diseases as a result of 

(a) 
generation of autoantibodies against various autoantigens, including oncoproteins ... tumour suppression genes (P53), proliferation associated antigens ... onconeural antigens ... cancer/testis antigens ..and rheumatic disease associated antigens... 

The clinical significance of the various autoantibodies is not clear. Anti-oncoprotein and anti-tumour suppression gene antigens are detected before the diagnosis of the cancer or in the early stages of the malignant disease, suggesting a potential diagnostic or prognostic role. 

Anti-onconeural antibodies are pathogenic and are associated with specific clinical neurological syndromes ...

(b) 
Paraneoplastic syndromes, a wide range of clinical syndromes, including classic autoimmune rheumatic diseases that develop among patients with cancer. 

(c)
Rheumatism after chemotherapy, a clinical entity characterised by the development of musculoskeletal symptoms after combination chemotherapy for malignancy. 

CONCLUSION: Autoimmune and rheumatic features are not rare among patients with malignancies. They are the result of various diverse mechanisms and occasionally they may be associated with serious clinical entities.
&&url PMID: 11302861


<b>Neoplasia and the coeliac syndrome in adults.</b>
&&url PMID: 4178419 


<b>Celiac disease and malignancy.</b>

Fifty-five patients with celiac disease and coexistent malignant disease (27 lymphoma, 28 other malignancies) are described.... The presentations of these malignancies were no different from their presentations in non-celiac patients, ...
&&url PMID: 7392945


<b>Myasthenia Gravis/thymectomy and malignancy.</b>

Three hundred ninety patients who underwent thymectomy for myasthenia gravis (MG) were followed up to investigate the development of associated malignancies. There were 102 patients with thymoma and 288 without thymoma. ...Our findings suggest that the presence of thymoma facilitates the occurrence of extrathymic malignancy, and that thymectomy never enhances the occurrence of malignancy but possibly inhibits it.
&&url PMID: 8043287
