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Lung Cancer (Carcinoma) Markers
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Lung Cancer (Carcinoma) Markers

Lung cancer is the malignant transformation and expansion of lung tissue, and is the most lethal of all cancers worldwide, responsible for 1.2 million deaths annually. It is caused predominantly by cigarette smoking, and predominantly affected men, but with increased smoking among women, it is now the leading cause of death due to cancer in women. However, some people who have never smoked still get lung cancer. Current research indicates that the factor with the greatest impact on risk of lung cancer is long-term exposure to inhaled carcinogens. The most common means of such exposure is air pollution and tobacco smoke.

Treatment and prognosis depend upon the histological type of cancer, the stage (degree of spread), and the patient's performance status. Treatments include surgery, chemotherapy, and radiotherapy.


  • recognizes heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP-A2/B1) can frequently detect lung cancer in exfoliated sputum epithelial cells 1-2 years earlier than routine chest X-ray or sputum cytomorphology. PMID: 11714531


  • a novel serological and histochemical marker for lung cancer. PMID: 15623614

AGNA (Anti-glial nuclear antibody)

  • marker of lung cancer-related paraneoplastic neurological syndromes. PMID: 15949849


  • hypermethylation of ASC/TMS1 is a marker for late-stage lung cancer and, in sputum, could predict prognosis in patients resected for early-stage disease. PMID: 16778195


  • a useful diagnostic marker for well-differentiated fetal adenocarcinoma of the lung. PMID: 17173289

CA 125

  • can be used as an adjunctive test in the management of patients with lung cancer patients. PMID: 1845935


  • serial measurement of plasma calcitonin is useful in the management of the patient with small cell carcinoma of the lung. PMID: 6267098

Cathepsin K

  • selectively expressed in the stroma of lung adenocarcinoma but not in bronchioloalveolar carcinoma. A useful marker of invasive growth. PMID: 16690483


  • an independent prognostic marker of survival in nonsmall cell lung cancer patients. PMID: 12610508


CEA (carcinoembryonic antigen)

  • serum CEA level can be a predictive factor for the efficacy of gefitinib treatment while it is also a prognostic factor for advanced non-small cell lung cancer (NSCLC) patients undergoing this treatment. PMID: 15939264

COX-2 (Cyclooxygenase-2)

  • a marker of poor prognosis in stage I non-small cell lung cancer. PMID: 11309334


  • may be a marker of choice for screening and monitoring of lung cancer, particularly squamous cell carcinoma. PMID: 8933183


  • a soluble fragment of cytokeratin 19 in serum of patients with NSCLC. It can be used as a useful tumor marker of non-small cell lung carcinoma (NSCLC). PMID: 11776818
  • a tumor marker that helps to establish the diagnosis and differentiation of cell type and evaluation of response to therapy in patients with non-small cell lung carcinoma (NSCLC). PMID: 11479694
  • a sensitive and specific tumor marker of non-small cell lung cancer, especially of squamous cell carcinoma. PMID: 11263296
  • may be a useful tumor marker in NSCLC, especially in carcinoma planocellulare. CYFRA 21-1 may also be useful in identification of the preoperative stages of diseases and the postoperative monitoring of NSCLC. PMID: 9887620
  • For patients with NSCLC, especially in squamous cell carcinoma, CYFRA 21-1 is not only a sensitive and specific tumor marker, but also may be a useful adjunctive marker for disease monitoring. PMID: 8635383
  • may be a useful tumor marker in NSCLC, especially in squamous cell carcinoma. However, CYFRA 21-1 cannot be used for the diagnosis of early stage disease of NSCLC. CYFRA 21-1 may also contribute to the monitoring of NSCLC. PMID: 8709175
  • has high sensitivity, specificity and positive predictive value in the diagnostics of SQCLC. Sensitivity of CYFRA 21-1 is significantly higher than sensitivity of CEA in this setting. PMID: 8841502
  • The data confirm the high sensitivity and specific of Cyfra 21-1 for the differential diagnosis between malignant and non-malignant pulmonary diseases as well as small cell and non-small cell lung cancer. PMID: 7533887
  • is of value in diagnosis of lung cancer, particularly squamous cell carcinoma. PMID: 9658744
  • Cyfra 21-1 and CEA appeared equally useful for evaluating patients with NSCLC. PMID: 8806188
  • Cyfra 21-1 is a new marker of lung cancer. PMID: 9296767
  • may be satisfactorily employed in the differential diagnosis between malignant and benign lung diseases in association with other clinical and radiological data. PMID: 7540561


  • a reliable marker of low-stage clinically aggressive lung carcinomas. PMID: 15736468


  • methylation of FHIT is a useful biomarker of biologically aggressive disease in patients with NSCLC. PMID: 15042681


  • Serum gamma-enolase value is a useful tumor marker for staging and monitoring treatment of patients with lung cancer, and serum gamma/alpha + gamma value may be useful for differential diagnosis of SCCL from non-SCCL or in differentiating lung cancers possessing neuroendocrine features from other lung cancers. PMID: 3036329

GRP (gastrin-releasing peptide)

  • plasma GRP level could be a useful tumor marker in small cell lung carcinoma (SCLC) patients. PMID: 2169019
  • known to be a very common product of small cell lung carcinoma (SCLC). PMID: 2535962


  • Smokers with the GST-mu enzyme have approximately one-third of the risk for lung carcinoma of smokers without the enzyme. PMID: 8485718

HDGF (Hepatoma-derived growth factor)

  • a useful prognostic marker for patients with completely resected NSCLC and it may play a critical role in the pathobiology of lung cancer through its mitogenic and angiogenic activities. PMID: 15870924

Histidine Decarboxylase

  • useful to distinguish between small cell lung carcinoma and non-neuroendocrine carcinoma and to demonstrate neuroendocrine differentiation. PMID: 12527716


  • the presence of HPV DNA in the blood circulation may serve as a feasible risk marker of lung cancer. PMID: 12627521


  • superior to other tumor markers in lung cancer diagnosis. PMID: 17052260
  • gene amplification is an important mechanism for hTERT overexpression in lung adenocarcinoma and is an independent poor prognostic marker for disease-free survival in NSCLC. PMID: 16641908


  • a candidate marker of neuroendocrine differentiation of human lung tumors. PMID: 8364910


Keratin 7

  • useful in differentiating between squamous cell carcinoma and adenocarcinoma of the lung and it may be particularly useful in making the correct diagnosis in small lung biopsy specimens. PMID: 7679658


  • seems promising in identifying low and high grade disease in the initial stage of lung cancer. PMID: 9783030


  • the immunohistochemistry for KM195 may be a more useful marker over CAM 5.2 for the diagnosis of pulmonary adenocarcinoma. PMID: 8865122


  • may be useful as a prognostic marker for patients with stage I primary lung adenocarcinoma. Conversely, use of this marker and subtyping of lung adenocarcinomas reflect the prognosis of the disease. PMID: 8377507


  • The presence of K-ras point mutations defines a subgroup of patients with lung adenocarcinoma in whom the prognosis is very poor and disease-free survival is not usually long despite radical resection and a small tumor load. PMID: 2199829

LCAP (Lung Cancer Associated Protein)

  • as detected by MAb TRD-L1 is a potentially useful marker for the evaluation of patients with lung cancer. PMID: 9342632
  • a new and potentially useful marker for the evaluation of patients with lung cancer. PMID: 1855201

LDH (lactate dehydrogenase)

  • the combined determination of serum LDH and NSE levels gives valuable data on the primary tumor mass and its proliferative activity in small cell lung cancer. PMID: 2849799

LSA (lipid-bound sialic acid)

  • serum LSA may be a useful biochemical marker in lung cancer patients. PMID: 2077205


  • a potential diagnostic method for detection of micrometastases in lymph nodes of non-small-cell lung-cancer (NSCLC) patients. PMID: 11251963

MAP-2 (Microtubule-associated protein 2)

  • recommend to be added to immunohistochemical panels to separate non-neuroendocrine from neuroendocrine lung tumors. PMID: 11557784


  • a promising marker for the diagnosis of primary lung adenocarcinoma. PMID: 12698189

NCAM (neural cell adhesion molecules)

  • NCAM is, along with NSE, a potential tumor marker for with small cell lung cancer (SCLC). PMID: 8391379
  • a surface marker for human small cell lung cancer cells. PMID: 2165922


  • a novel marker for cell-mediated immunity in patients with pulmonary tuberculosis and lung cancer. PMID: 11243956

NRSF (neuron-restrictive silencer factor)

  • NRSF splice variant represents a specific clinical marker that could prove useful in detection of the majority of SCLCs. PMID: 10766169

NSE (Neuron-specific enolase)

  • the most frequently elevated tumor marker for patients with small cell lung cancer (SCLC) at diagnosis. PMID: 8391379
  • could be of aid in the early diagnosis of solitary pulmonary nodules and lung cancer. PMID: 8062188
  • a useful tumor marker for small cell lung cancer. PMID: 2155054
  • demonstrated immunohistologically both in small cell and non-small cell bronchial carcinoma tissue, but high NSE levels were predominantly present in small cell carcinomas. PMID: 2846253
  • a marker for lung carcinoma which exhibit the properties of neuroendocrine tumors and is not a marker for histogenesis of small cell carcinoma of the lung. PMID: 6086970
  • may be a useful marker for monitoring the clinical course of lung carcinoma, especially of SCCL. PMID: 6305752
  • a well known marker of small cell lung cancer, is also a useful marker in non-small cell lung cancer (NSCLC) and a significant predictor of survival, independently of the other prognostic factors. PMID: 12928122
  • one of the most widely used tumor markers in small-cell lung carcinoma (SCLC). PMID: 7964990
  • Serum NSE determination seems to be a valuable tool for the diagnosis of small cell carcinoma. PMID: 2983452
  • There was a good correlation between serum NSE levels and the clinical course of patients with small-cell carcinoma of lung (SCCL). PMID: 6095430
  • a useful diagnostic marker for small cell lung cancer pleurisy. PMID: 2537710

Osteopontin (OPN)

  • large increase in OPN expression in tumors compared with normal tissue and its association with survival suggest a role for OPN in lung tumorigenesis. PMID: 15014008


  • a possible marker of advanced stage in non-small cell lung cancer. PMID: 11815997


  • expression occurs in both non-neoplastic and neoplastic epithelium of the human respiratory tract. The increased expression of p31 in the peripheral lung may be potentially informative as to what critical cell populations are involved in the development of invasive cancers. PMID: 8696723


  • Analysis of p53 gene mutations was thus useful in distinguishing second primary lung cancers from recurrent tumors. PMID: 9305187

p63 and TTF-1

  • appear to be useful for differentiating small cell lung carcinoma (SCLC) from lung poorly differentiated squamous cell carcinoma (PDSCC) in formalin-fixed and alcohol-fixed, formalin-postfixed material. PMID: 12760288

PAI-2 (plasminogen activator inhibitor 2)

  • may be useful as a marker for evaluating the prognosis of lung cancer. PMID: 9743310


  • specifically associated with lung cancer development and may serve as a potential marker for the detection of lung cancer. PMID: 10487828

PKP3 (plakophilin 3)

  • might hold promise for development of a new therapeutic and diagnostic strategy for clinical management of lung cancers. PMID: 16103059

Progastrin-releasing peptide (proGRP)

  • a precursor of gastrin-releasing peptide, a hormone which is secreted from neuroendocrine cells. It has been shown to be a useful serum marker for small cell lung cancer. PMID: 17287611

Pro-GRP (Gastrin-releasing peptide )

  • a member of the bombesin family of peptides, may be a potential tumor marker for small cell lung carcinoma. PMID: 12820319
  • the determination of serum ProGRP(31-98) was a reliable marker for small-cell lung carcinoma (SCLC). PMID: 7720242
  • serum Pro-GRP has high specificity and could be a useful marker of SCLC for treatment monitoring and prognosis. PMID: 10461062


  • the determination of serum ProGRP(31-98) levels plays an important role in the diagnosis and treatment of small cell lung carcinoma (SCLC) patients. PMID: 8174119
  • the determination of serum ProGRP(31-98) levels plays an important role in the diagnosis and treatment of SCLC patients. PMID: 8630283


  • an independent prognostic marker of survival in non-small-cell lung cancer patients. PMID: 15956972


  • ras gene mutations may be prognostic, especially in the early stage adenocarcinoma of the lung. PMID: 1581907


  • determination at onset of pleural effusion is informative for both diagnosis and outcome prediction in lung cancer patients. PMID: 16773186


  • expression of the S100A2 protein in stage I NSCLC indicates poor prognosis and may be used to identify patients with early-stage NSCLC who might benefit from adjuvant treatment. PMID: 15800916

SAG (sensitive to apoptosis gene)

  • SAG gene expression in non small cell lung cancer (NSCLC) may be a useful prognostic marker. PMID: 11668520



  • play a role in the carcinogenesis, progression, and prognosis of primary lung cancer. PMID: 15010875


  • a sensitive and specific marker for squamous bronchogenic carcinoma. PMID: 9699184


  • the expression of survivin in tumor cells is a factor of poor prognosis in patients with small adenocarcinoma of the lung. PMID: 12066218

TACC3 (transforming acidic coiled-coil containing protein 3)

  • a novel independent prognostic marker in non-small cell lung cancer. PMID: 16930330

T antigen (Thomsen-Frienden-reich antigen)

  • The presence of T antigen immunoreactivity in tumor cells is a useful marker of prognosis in patients with pulmonary adenocarcinoma. PMID: 10023001


  • detection of telomerase protein in noncancerous bronchial epithelia will become a useful marker detecting high-risk patients for lung cancer development. PMID: 16266979

Tenascin (Tn)-C

  • may play an important role in angiogenesis of patients with NSCLC, and the determination of serum Tn-C may be useful in predicting intratumoral vasculature and patients' prognosis. PMID: 15816617

TGF beta 1

  • Elevated plasma TGF beta 1 levels occur frequently in patients with lung cancer. In those patients with an elevated plasma TGF beta 1 level at diagnosis, monitoring this level may be useful in detecting both disease persistence and recurrence after therapy. PMID: 9017584


  • maybe a novel latent malignant marker in the lung cancer pathology. PMID: 16255990

TLP (Tumour Liberated Proteins)

  • a 214 kDa protein, isolated from lung cancer tissue, is a new tumour associated antigen of non-small cell lung cancer and could represent an useful tumour marker. PMID: 8694552

TTF-1 (thyroid transcription factor-1)

  • In tissue sections, TTF-1 is a sensitive marker for adenocarcinomas of lung and thyroid origin. In cytologic preparations, TTF-1 is a highly selective marker for pulmonary adenocarcinoma and also can have a role in the distinction between pulmonary adenocarcinoma and mesothelioma. PMID: 11601132

Tumor M2-PK

  • With the fuzzy logic method and a tumor marker panel (including the new marker Tumor M2-PK), a useful diagnostic tool for the detection of progression in lung cancer patients is available. PMID: 12820320


  • The combination of VEGF and CEA was superior to CEA alone in the early diagnosis of adenocarcinoma of the lung. PMID: 12521132

YB-1 (Y-box binding protein 1)

  • a negative prognostic marker in nonsmall cell lung cancer. PMID: 14738225
  • a novel marker of disease progression in non-small cell lung cancer. PMID: 11595709

Other Lung Cancer Markers

  • The combination of NSE and pro-GRP is more appropriate than other combinations in diagnosing small-cell lung cancer; the combination of CYFRA21-1, CEA and p53 antibody is the most valuable combination for diagnosing non-small-cell lung cancer. p53 antibody has the highest specificity for diagnosing lung cancer; CYFRA21-1 is the most valuable parameter for diagnosing squamous carcinoma. PMID: 15996327
  • Plasma DNA microsatellite panel as sensitive and tumor-specific marker in lung cancer patients. PMID: 12704670
  • Fuzzy logic-based tumor-marker profiles improved sensitivity in the diagnosis of lung cancer. PMID: 12109515
  • 18F-FDG coincidence imaging is a powerful tool for evaluating patients with lung lesions suggestive of malignancy. Although the determination of serum marker levels is less accurate than 18F-FDG coincidence imaging, the combination of a positive 18F-FDG coincidence result and positive tumor markers may be helpful in improving the diagnosis of lung cancers. PMID: 17274375
  • measuring multiple tumor markers was of clinical value in monitoring the clinical course of cancer patients as well as in assisting the diagnosis of lung cancer. PMID: 2018388plasma DNA may be a useful marker in patients with lung cancer. PMID: 2243459
  • quantitative cytosine methylation profiling can be used to identify molecular classification markers in lung cancer. PMID: 17108128
  • Increased collagenase activity in macrophages from bronchial lavage as a diagnostic marker of non-small cell lung cancer. PMID: 12554893
  • tetanus toxin labeling may become a useful diagnostic marker for SCLC cells in cytology. PMID: 2558117
  • Determinations of CABLA could thus be a potential and valuable marker for a subset of SCLC. PMID: 2556168
  • serum pseudouridine may be a useful biochemical marker in the patients with SCLC. PMID: 2822241
  • free EBV DNA can be detected in the serum of patients with LELC of the lung and further suggests the feasibility of its use for monitoring response to therapy in advanced cases. PMID: 11948104
  • the use of diacylglycerol measurement as a novel biomarker for early detection of lung cancer, and for monitoring recurrences after treatment. PMID: 8882982
  • For distinguishing between epithelioid mesothelioma and lung adenocarcinoma, the combination of CEA, calretinin and each WT1 or thrombomodulin was suggested to be the best panel of immunohistochemical markers. PMID: 17316414

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