The Expression Of PTEN And FHIT Protein In Lung Adenocarcinoma And In Lung Squamous Carcinoma

Objectives: Cancer is a multi-gene disorders and a multi-step, multi-factor complex process.Its genesis and development is the results of a series of genetic abnormalities and dynamic evolution of the activation of proto-oncogenes and inactivation of anti-oncogene. Lung cancer is one of the human common malignant tumor. China has a high incidence of lung cancer and also one country that has the highest mortality of this disease in the world. The total incidence of lung cancer in male accounts for first of all malignant tumors. PTEN is a recently discovered tumor suppressor gene. The study found that many tumors revelent with PTEN genetic alterations,such as gene mutation, deletion and over-methylation which suggest that PTEN gene mutations play an important role in tumor occurrence and development. PTEN has very complex function, for example,participate the normal embryonic development, induce apoptosis, cause cells in G1 phase arrest, inhibit cell migration, spreading and promote focal adhesion. FHIT protein expresses in all body's tissues, but its specific function in the body is unclear. It has found that the concentration of FHIT in animal cells was very sensitive to environmental change and stress response.It may be the signal system or alarm system to external stimuli in the regulation of cell proliferation, differentiation, apoptosis. Another study shows that FHIT gene plays an important role in apoptosis and cell cycle regulation. Import FHITcDNA to the tumor cells that short of FHIT gene which can lead to re-expression of FHIT protein may cause a increase in cell number arrested at S phase and G0/G1 phase and the number of apoptotic cells,but decrease carcinogenicity. This study was designed to detect the expression of FHIT and PTEN in normal tissue,lung squamous carcinoma tissue and lung adenocarcinoma tissue to explore the different occurrence and development mechanisms of the two kinds lung tumor and to explore the significance of these two proteins In the clinical pathology.It may provide a scientific theory to clinical treatment for lung cancer through this study.Materials and methods: In this study, PTEN and FHIT protein in lung cancer organizations of squamous carcinoma and lung adenocarcinoma patients are analyzed by immunohistochemical staining Specimens are taken from fresh cancer tissues and adjacent tissues in part of the surgical treatment of patients with lung squamous carcinoma and lung adenocarcinoma suffered from Thoracic Surgery in the Fourth Hospital of Hebei Medical University, in 2009.The species include cancer tissue 63 cases, 63 cases of adjacent tissue, male 40 cases, 23 female, aged 46 to 75 years old, with an average age of 64 year.sold.Histological.classification:39squamous.carcinoma,24adenocarcino-ma, 27well-differentiated and moderately differentiated squamous carcinoma cases, 12 cases of poorly differentiated squamous carcinoma, adenocarcinoma 17 cases, seven cases of poorly differentiated adenocarcinoma. 36 cases with lymph node metastasis and 27 patients without lymph node metastasis. All the patients did not receive preoperative chemotherapy, radiotherapy and other treatments. 20 cases of normal lung tissue were used as control group. All specimens were cut into 5um paraffin sections consecutivly,and than go through biopsy dewaxing, inactivated, antigen retrieval,immunohistochemistry staining, stained, dehydration and mounting in turn .PBS solution was saved as negative control and positive control added anti-antibody only. Data processing: Each slice of all specimens was randomly counted 1000 cells in 10 visions through Motic Med 6.0 digital medical image analysis system with the same magnification,and calculated the percentage of positive cells(the standard was positive cells≥25% ).The expression of PTEN and FHIT antigen were indicated by the mean optical density (OD) after positive cells stained. A database was established after all data entered in computer and was analyzed by SPPSS (10.0) statistical analysis software. The rate of PTEN, FHIT protein was analyzed by Chi-square test and Fisher probabilities test. The average optical density (OD) value was analyzed by t test. The association between PTEN with FHIT was analyzed by Chi-square test of matched-pairs fourfold table, test level (α= 0.05).Results:1 The positive expression rate of PTEN in the normal lung tissue was 85.0% (17/20), significantly higher than lung cancer 52.4% (33/63), the difference was significant (P <0.05). The positive expression rate of PTEN in squamous carcinoma was 58.9% (23/39), and the rate in adenocarcinoma was 41.7% (10/24). Thus there was no significant difference between the two(P> 0.05). The positive expression rate of PTEN in well-differentiated squamous cell carcinoma and moderately differentiated cancer, was 77.8% (21/27)and the rate in poorly differentiated squamous carcinoma was 16.7% (2 / 12),so the differences were significant (P <0.05).The positive expression rate of PTEN in well-differentiated adenocarcinoma 52.9% (9 / 17) and the rate in poorly differentiated adenocarcinoma was 14.3% (1 / 7),so there was no difference significantly (P> 0.05). The positive expression rate of PTEN in the lung cancer tissues with absence of lymph node metastasis was 66.7% (18/27) and the rate in lung cancer tissues with lymph node metastasis was 41.7% (15/36) ,so there was significant difference (P <0.05).2 The positive was 87.2% (34/39) compared with rate of 58.9% in squamous cell carcinoma(23/39).So there existed significant difference (P <0.05). The positive expression rate of PTEN in adjacent adenocarcinoma tissues was 79.2% (19/24), compared with rate of 41.7% (10/24) in adenocarcinoma. So the difference was significant (P <0.05).3 The positive expression rates of PTEN in men and women in were 50% (20/40) and 56.5% (13/23);in group older than 60 years and youger than 60 years were 42.9% (6 / 14) , 55.1% (27/49); in the smoking group and non-smoking group were 46.7% (14/30), 57.6% (19/33). The differences in the the groups were no statistics significant (P> 0.05).4 The positive expression rate of FHIT in the normal lung tissue was 95.0%(19/20), significantly higher than lung cancer 49.2%(31/63), the difference was significant (P <0.05). The positive expression rate of FHIT in squamous carcinoma was 35.9%(14/39), and the rate in adenocarcinoma was 70.8%(17/24). Thus there was significant difference between the two(P<0.05). The positive expression rate of PTEN in well-differentiated squamous cell carcinoma and moderately differentiated cancer was 44.4%(12/27)and the rate in poorly differentiated squamous carcinoma was 16.7% (2 / 12),so there was no significant difference (P <0.05).The positive expression rate of FHIT in well-differentiated adenocarcinoma 70.6%(12/17) and the rate in poorly differentiated adenocarcinoma was 71.4%(5/7),so there was no difference significantly (P> 0.05). The positive expression rate of FHIT in the lung cancer tissues with absence of lymph node metastasis was 59.3%(16/27)and the rate in lung cancer tissues with lymph node metastasis was 41.6%(15/36) ,so there was no significant difference (P <0.05).5 The positive expression rate of FHIT in adjacent squamous carcinoma tissues was 51.3%(20/39), compared with rate of 35.9%(14/39) in squamous carcinoma.So there existed no significant difference (P <0.05). The positive expression rate of FHIT in adjacent adenocarcinoma tissues was 87.5%(21/24), compared with rate of 70.8%(17/24) in adenocarcinoma. So there was no significant difference also (P <0.05).6 The positive expression rates of FHIT in men and women in were 50%(20/40),47.8%(11/23);in group older than 60 years and youger than 60 years were 50.0%(7/14),49.0%(24/49). The rates in the smoking group and non-smoking group were 23.3%(7/30),72.7%(24/33). There were significant difference in the fist two groups,but no in the last(P> 0.05).7 The relevance of PTEN and FHIT: PTEN positive expression in 33 cases of carcinoma,in which 20 cases were positive expression of FHIT. 20 cases were positive expression of PTEN in FHIT expression cancer tissues. 19 cases were negative expression of PTEN and FHIT.There were no differences between them through matched-pairs variance analysis (P>0.05)Conclusions:1 The expression of PTEN in normal lung tissue is higher than lung cancer tissues. PTEN expression has no revelent with pathological types of lung cancer, but asssotiated with the degree of differentiation of lung cancer and lymph node metastasis, which can be used as prognostic indicators for lung cancer.2 It showed strong expression and a higher expression rate of FHIT in normal lung tissue. FHIT expression was revelent with pathological types of lung cancer, but not assotiated with lymph node metastasis and the differentiation degree of squamous carcinoma and adenocarcinoma. Considering a higher expression rate in adenocarcinoma, FHIT may not be an important gene in canceration of adenocarcinoma.3 The expression of PTEN and in squamous carcinoma and adenocarcinoma tissue had no revelent with age and sex.The expression of FHIT was related to smoke,but PTEN was not.It showed that FHIT might be the carcinogenesis of smoke.4 There were 20 cases of positive expression of FHIT in 30 cases of positive expression of PTEN and there were 19 cases of negetive expression of FHIT in 30 cases of negetive expression of PTEN.There were no significant diffrences,but had associativity.