Transplantation and tumor

• Transplantation


  Transfer of tissue or organ from one individual to another
• Transfusion


  Transfer of blood from one individual to another
• Antibodies are responsible for transfusion reactions
• Rejection of transplanted tissue is mediated predominantly by T cells
• Types of Transplantation

  • Autologous graft (Autograft)
  • Syngeneic graft (Syngraft, Isograft)
  • Allogeneic graft (Allograft, Homograft)
  • Xenogeneic graft (Heterologous graft, Heterograft)
• Autologous graft (Autograft)

  Graft or transplant from one area to another on the same individual, no immune response is induced against it
• Syngeneic graft (Syngraft, Isograft)


  Graft or transplantation of cells, tissue, or organ from one person to another who is syngeneic (genetically identical) to the donor, does not mount an immune response against it
• Allogeneic graft (Allograft, Homograft)


  Graft or transplant from one individual to another with a different genetic make-up, within the same species, graft is recognized by recipient as foreign and is immunologically rejected
• Xenogeneic graft (Heterologous graft, Heterograft)


  Graft between a donor and a recipient from different species, transplant is recognized as foreign and immune response mounted against it will destroy or reject graft
• Clinical Phases of Rejection

  • Hyperacute Rejection
  • Accelerated Rejection
  • Acute Rejection
  • Chronic Rejection
• Hyperacute Rejection


  Occurs within a few minutes to a few hours of transplant, pre-existing antibodies to donor HLA antigens activate complement system followed by platelet activation and deposition causing swelling and interstitial hemorrhage in the transplanted tissue, no therapy for successful prevention or termination
• Acute Rejection


  Seen in recipient who has not previously been sensitized to transplant, reaction may begin a few days after transplantation with a complete loss of kidney function within 10 - 14 days, accompanied by a rapid decrease in renal function
• Chronic Rejection


  Months to years, mixed humoral and cellular mechanism, still hard to manage, caused by both antibody and cell mediated immunity, characterized by slow, progressive renal failure in kidney transplantation
• Laboratory Tests

  • ABO Blood Typing
  • Tissue Typing (HLA Matching)
  • Lymphocytotoxicity Test
  • Mixed Leukocyte Reaction
  • Screening for Presence of Preformed Antibodies to Allogeneic HLA
  • Crossmatching
• Graft-Vs-Host Disease

  Can occur when immunocompetent tissue (fresh whole blood, thymus, or bone marrow) is transplanted into an immunocompromised host, T cells from the transplant recognize the host MHC molecules as non-self and attack the host, a type IV hypersensitivity reaction
• Situations leading to Graft-Vs-Host Disease

  • Allograft in a recipient in whom specific immunological tolerance has been induced
  • Retardation of growth
  • Diarrhea, Hepatosplenomegaly
  • Lymphoid atrophy
  • Anemia
  • Terminating fatally, Syndrome is called RUNT Disease
• Classification of Transplants based on nature of organs

  • Kidney
  • Liver
  • Heart
  • Bone marrow
  • Skin
• Classification of Transplants based on Anatomical Site

  • Orthotropic - skin graft
  • Heterotypic - on abnormal site (e.g. thyroid gland in subcutaneous region)
• One set of parents can produce four combinations of offspring, therefore each brother or sister has a one-in-four chance of carrying the exact same HLA antigens as the patient
• Tumor


  An abnormal cell mass resulting from excessive cell growth & division, benign - composed of slowly growing cells that are well differentiated & organized, malignant - disorganized masses that are rarely encapsulated
• Cancer


  Multigene disease which arises as a result of mutational and epigenetic changes coupled with activation of complex signaling networks, involves alteration of proto-oncogenes, tumor suppressor genes, and other genes contributing to development of cancer genotype and phenotype
• Tumor Marker


  Substance produced by a tumor or by the host in response to a tumor which is used to differentiate a tumor from normal tissue or to detect the presence of a tumor based on measurements in blood or secretions, ideal tumor marker should be highly specific, highly sensitive, specific to a particular organ, correlate with the prognosis, and have a reliable prediction value
• Historical Background of Tumor Markers

  • 1846 - Bence-Jones Protein
  • 1940 - Acid Phosphatase
  • 1960 - Immunoassay
  • 1963 - Alpha-fetoprotein
  • 1965 - Carcinoembryonic antigen
  • 1970 - Oncogenes
  • 1975 - Monoclonal antibodies
  • 1980 - CA 125, PSA (Prostate Specific Antigen), Carbohydrate antigens
  • 2001 - Microarrays, Mass Spectrometry, Neural Networks, Multiparametric Analysis
• Enzymes as Tumor Markers

  • Alcohol Dehydrogenase & Aldolase - Liver Cancer
  • Alkaline Phosphatase - Bone, Liver, Leukemia
  • Prostatic Acid Phosphatase - Prostate
  • Neuron Specific Enolase - Small Cell Lung Cancer, Neuroblastoma, Melanoma
  • Lactate Dehydrogenase - Lymphoma, Leukemia
• Hormones as Tumor Markers

  • ACTH - Cushing's syndrome, Lung Cancer
  • ADH - Lung, Adrenal Cortex, Pancreatic
  • Bombesin - Lung
  • Calcitonin - Medullary Thyroid Carcinoma
  • Vasoactive Intestinal Peptide - Pheochromocytoma, Neuroblastoma
  • Human Chorionic Gonadotropin - Choriocarcinoma, Embryonal
• Proteins as Tumor Markers

  • Beta 2 Macroglobulin - Multiple Myeloma, Chronic Myeloid Leukemia, Waldenstrom's Macroglobulinemia
  • C-Peptide - Insulinoma
  • Ferritin - Liver, Lung, Breast, Leukemia
  • Immunoglobulins - Multiple Myeloma, Lymphomas
  • Melanoma Associated Antigen - Melanoma
  • Des-Gamma-Carboxy Prothrombin - Hepatocellular
  • Soluble Mesothelin Related Peptides - Mesothelioma, Ovarian
• Carbohydrates or Mucin as Tumor Markers

  • CA-125 - Ovarian, Endometrial
  • CA-15-3 - Breast, Ovarian
  • CA-549 - Breast, Ovarian
  • CA-27.29 - Breast
  • Mucin-Like Carcinoma Associated Antigen (MCA) - Breast, Ovarian
  • DUPAN-2 - Pancreatic
• Blood Group Antigen Related Markers

  • CA 72-4 - Ovarian, Pancreatic, Stomach Cancer
  • CA 19-9 - Pancreatic, Gastrointestinal, Hepatic
  • CA 19-5 - Pancreatic, Gastrointestinal, Ovarian
  • CA 50 - Pancreatic, Gastrointestinal, Colon
  • CA 242 - Pancreatic, Gastrointestinal
• Prostate Specific Antigen (PSA)

  Only marker used to screen for a common type of cancer (prostate cancer), a single chain glycoprotein specific for prostatic tissue, gene encoding PSA has been sequenced & located on chromosome 19, a serine protease of the kallikrein family (KLK3), sandwich immunoassays are used to measure PSA
• Oncofetal Antigens

  • Alpha Fetoprotein (AFP) - Hepatocellular, Germ Cell Tumor
  • Carcinofetal Ferritin - Liver
  • Carcinoembryonic Antigen (CEA) - Colorectal, Gastrointestinal, Lung, Breast, Pancreatic
  • Squamous Cell Antigen - Cervical, Lung, Skin, Head, Neck
  • Tennessee Antigen - Colon, Gastrointestinal, Bladder
  • Cytokeratins
  • Tissue Polypeptide Antigen - Breast, Colorectal, Ovarian, Bladder
  • Tissue Polypeptide Specific Antigen - Cytokeratin 19 Fragments (prognostic marker for non-small cell lung cancer)
• Oncogenes


  Derived from proto-oncogenes that may be activated by dominant mutations, insertions, deletions, translocations, or inversions, most oncogenes code for proteins needed for proliferation, their activation leads to cell division, most oncogenes are associated with hematologic malignancies, such as leukemia & to a lesser extent solid tumor
• HER-2/neu (ERBB2)


  This gene codes for EGF family of tyrosine kinase receptors which are involved in cell proliferation, differentiation & survival, amplification of this gene is found in breast, ovarian & gastrointestinal tumors, HERCEPTIN treatment is administered only to those breast cancer patients who have HER-2/neu amplification, immunohistochemistry is used to detect increased expression, FISH is used for detection of gene amplification
• Oncogene erbB-2 gene


  Over expressed in 30% of breast cancers, correlation between positivity, positive auxiliary node status, reduced time to relapse and reduced overall survival
• BRCA I gene on Chromosome 17q


  Familial breast-ovarian cancer syndrome, breast cancer in early-onset breast cancer families, high risk screening
• Viral Biomarkers for Hepatocellular Cancer

  • Analysis of viral DNA or proteins or antibodies produced against viral proteins
  • HBsAG
  • HBsSG
  • Anti-HBV core-antigen
  • Anti-HBeAG, Anti-HbsAG
• Hepatitis B Virus promotes carcinogenesis through genetic instability generated by its common integration in host DNA
• Acute Rejection

  Around 10 – 30 days; Cellular Mechanism (CD4, CD8, NK, Macrophages); Seen in recipient who has not previously been sensitized to transplant.; Common type of rejection experienced by individuals for whom transplanted tissue is a mismatch.