| Objectives1.To analyze the pathological features of early lung adenocarcinoma by the image analysis and discuss the value of image analysis parameters in the pathological subtypes and clinical T stages of early lung adenocarcinoma.2.To explore the relationship between the early lung adenocarcinoma of PET-CT maximum Standardized Uptake Value(SUVmax)and image analysis parameters and its correlation with clinical pathological features.3.To explore the relationship between the early lung adenocarcinoma EGFR gene mutation and image analysis parameters and its correlation with clinical pathological features.Methods1.Collecting a total of 94 patients confirmed as early lung adenocarcinoma with a diameter of less than or equal to 3cm from Department of Pathology of Nanfang Hospital,pathological techniques routinely embed the slides and HE staining by paraffin,referencing new classification criteria of lung adenocarcinoma in 2015,classifying and recording pathological result of 94 patients by blind method,divided into adenocarcinoma in situ,minimally invasive adenocarcinoma,lepidic adenocarcinoma.Referring to the International Lung Cancer Research Association 8th edition of lung cancer TNM staging criteria,the paper divides the staging of early lung adenocarcinoma with diameter?3 cm into Tis(Adenocarcinoma in situ),T1a(minimally invasive adenocarcinoma,Maximum tumor diameter?1cm),T1b(Maximum tumor diameter?2cm),T1c(Maximum tumor diameter?3cm).Each case requires the photographing of 10 relatively intact glands under 20x microscope view and 100-150 cells in the corresponding gland under 40x microscope view.The author tests and calculates the image through the Image-Pro Plus image analysis software,selecting image analysis parameters include generalized line reference number density of cancer cells in glands,nucleolus occurrence rate in glands,gland cell adhesion rate,the maximum distance between glands,the minimum distance between glands and nucleus morphological parameters(long axis,short axis,perimeter,area,roundness and regular form factor).2.From the 94 patients confirmed as early lung adenocarcinoma with a diameter of less than or equal to 3 cm by Nanfang Hospital Pathology Department,the paper retrospectively analyzed the imaging data of 57 patients with early lung adenocarcinoma who underwent preoperative PET/CT examination and the correlation between SUVmax and image analysis parameters(generalized line reference number density of cancer cells in glands,nucleolus occurrence rate in glands,gland cell adhesion rate,the maximum distance between glands,the minimum distance between glands and nucleus morphological parameters(long axis,short axis,perimeter,area,roundness and regular form factor))and its application in pathological subtypes and clinical T stages of early lung adenocarcinoma.3.From the 94 patients confirmed as early lung adenocarcinoma with a diameter of less than or equal to 3 cm by Nanfang Hospital Pathology Department,the paper retrospectively analyzed the imaging data of 51 patients with early lung adenocarcinoma who underwent EGFR gene examination and the correlation between EGFR gene mutation and image analysis parameters(generalized line reference number density of cancer cells in glands,nucleolus occurrence rate in glands,gland cell adhesion rate,the maximum distance between glands,the minimum distance between glands and nucleus morphological parameters(long axis,short axis,perimeter,area,roundness and regular form factor))and its application in pathological subtypes of early lung adenocarcinoma.Results1 Test results of image analysis parameters in various pathological subtypes and clinical T stages.First,Test results of image analysis parameters of early lung adenocarcinoma in various pathological subtypes:Generalized line reference number density of cancer cells in glands,nucleolus occurrence rate,gland cell adhesion rate,the maximum distance between glands,nucleus area,nucleus long axis,nucleus short axis and nucleus perimeter have differences in situ,minimally invasive adenocarcinoma and lepidic adenocarcinoma.Nucleus roundness and regular form factor have no differences in situ,minimally invasive adenocarcinoma and lepidic adenocarcinoma.The analysis result of each parameter is as follows:Generalized line reference number density of cancer cells in glands,gland cell adhesion rate:lepidic adenocarcinoma>minimally invasive adenocarcinoma>adenocarcinoma in situ.Changes in the number of cancer cells and cell adhesion have the following characteristics:(1)Generalized line reference number density of cancer cells in glands shows a continuously increasing trend among adenocarcinoma in situ,minimally invasive adenocarcinoma and lepidic adenocarcinoma.Adenocarcinoma in situ is the most sparse.Lepidic adenocarcinoma is the most dense.Minimally invasive adenocarcinoma is approximately 1.4 times as adenocarcinoma in situ.Lepidic adenocarcinoma is approximately 2 times as minimally invasive adenocarcinoma.(2)Gland cell adhesion rate shows a continuously increasing trend among adenocarcinoma in situ,minimally invasive adenocarcinoma and lepidic adenocarcinoma.Adenocarcinoma in situ is the highest.Lepidic adenocarcinoma is the lowest.Minimally invasive adenocarcinoma is approximately 2 times as adenocarcinoma in situ.Lepidic adenocarcinoma is approximately 1.6 times as minimally invasive adenocarcinoma.Therefore,when generalized line reference number density of cancer cells in glands increases and there is a phenomenon of high gland cell adhesion rate at the same time,the gland has the characteristics of invasive adenocarcinoma.Nucleolus occurrence rate in glands:Lepidic adenocarcinoma>minimally invasive adenocarcinoma,lepidic adenocarcinoma>adenocarcinoma in situ.Changes in the number nucleolus in the gland:(1)Nucleolus occurrence rate in glands of lepidic adenocarcinoma is higher than nucleolus occurrence rate in glands of minimally invasive adenocarcinoma.Lepidic adenocarcinoma is approximately 1.43 times as minimally invasive adenocarcinoma.Protein synthesis is most active in lepidic adenocarcinoma.(2)There was no significant difference in nucleolus occurrence rate in glands between adenocarcinoma in situ and minimally invasive adenocarcinoma.The maximum and minimum distance between glands:adenocarcinoma in situ and minimally invasive adenocarcinoma are bigger than lepidic adenocarcinoma.There was no significant difference in the minimum distance between glands between pathological subtypes.The results of the analysis are as follows:the maximum distance between glands of adenocarcinoma in situ and minimally invasive adenocarcinoma is bigger than adenocarcinoma in lepidic adenocarcinoma's.Its glands are more sparser in situ and minimally invasive adenocarcinoma than that of lepidic adenocarcinoma.There was no significant difference in the minimum distance between glands between adenocarcinoma in situ and minimally invasive adenocarcinoma,whose interstitial structure is similar.Nucleus morphological parameters:the long axis,short axis,perimeter,and area of the nucleus of minimally invasive adenocarcinoma cells and lepidic adenocarcinoma are slightly larger than those of the adenocarcinoma in situ.The nucleus long axis,short axis,perimeter,area are the smallest in situ.There was no significant difference in long axis,short axis,perimeter,area of minimally invasive adenocarcinoma and lepidic adenocarcinoma.There was no significant difference in nucleus roundness and regular form factor among various pathological subtypes.Regular form factor is 0.96.Nucleus roundness is range 1.10 to 1.17.They are all close to 1.The shape of the cell nucleus of various pathological subtypes is relatively regular,relatively close to a circle or an ellipse,and the heterogeneity between the nucleus is not large.Second,test results of image analysis parameters in various clinical T stages:there was significant difference in generalized line reference number density of cancer cells in glands,nucleolus occurrence rate,gland cell adhesion rate,the maximum distance between glands,nucleus area,nucleus long axis,nucleus short axis and nucleus perimeter among various pathological subtypes.Nucleus roundness,regular form factor,the minimum distance between glands have no differences in Tis stages,T1a stages,T1b stages,T1c stages.The analysis result of each parameter is as follows:Generalized line reference number density of cancer cells in glands:Tis<T1a<T1b?Tis<T1c;Gland cell adhesion rate:Tis<T1a<T1b?Tis<T1c?T1a<T1c.Changes in the number of cancer cells and cell adhesion have the following characteristics among various clinical T stages:(1)Generalized line reference number density of cancer cells in glands shows a continuously increasing trend between Tis and T1a,T1a and T1b,T1a is approximately 1.4 times asTls.T1a is approximately 2 times as T1b.(2)Gland cell adhesion rate shows a continuously increasing trend between Tis and T1a,T1a and T1b.T1a is approximately 2.1 times as T1s.T1a is approximately 1.5 times as T1b.(3)Tumor diameter increases by 1cm between T1b and T1c.There was no significant difference in generalized line reference number density of cancer cells in glands,gland cell adhesion rate between T1b and T1c.Nucleolus occurrence rate in glands among various clinical T stages:Tis<T1c?T1a<T1cN T1b<T1c.T1c has the highest incidence of nucleolus occurrence rate in glands.Tis is approximately 2.4 times as T1c,T1a is approximately 2.1 times as T1c,T1b is approximately 1.7 times as T1c.The maximum and minimum distance between glands:There was no significant difference in the minimum distance between glands among Tis stages,T1a stages,T1b stages,T1c stages,but the maximum distance between glands is statistically significant.The maximum distance between glands of Tis stages is the largest,the width of glands is the largest,and its glands are sparse.Among various clinical T stages,the nucleus long axis,short axis,perimeter and area had statistical significance,whose changes have the following characteristics:(1)The nucleus long axis,short axis,perimeter and area of T1c are the largest,the nucleus long axis,short axis,perimeter and area of T1s are the smallest.(2).The changes of the long axis,short axis,perimeter,and area were not obvious among T1a?T1b and T1c.There was no significant difference in nucleus roundness and regular form factor of cell among various clinical T stages.Regular form factor is 0.96.Nucleus roundness is range 1.10 to 1.20..They are all close to 1.The shape of the cell nucleus of various clinical T stages is relatively regular,relatively close to a circle or an ellipse,and the heterogeneity between the cell nucleus is not large.2 Analysis results of correlation between image analysis parameters and SUVmax and application of SUVmax in pathological subtypes and clinical T stages.First,there is a moderate positive correlation between nucleolus occurrence rate in glands,cell nucleus short axis,cell nucleus perimeter and SUVmax.There is a weak negative correlation between the maximum distance between glands and SUVmax.There is no correlation between generalized line reference number density of cancer cells in glands,cell nucleus roundness,regular form factor and SUVmax.Second,SUVmax values in pathological subtypes of early lung adenocarcinoma:There was no significant difference between SUVmax of adenocarcinoma in situ and minimally invasive adenocarcinoma.SUVmax of adenocarcinoma in situ and lepidic adenocarcinoma and SUVmax of minimally invasive adenocarcinoma and lepidic adenocarcinoma had significant difference.The distribution of SUVmax in early lung adenocarcinoma:(1)SUVmax of lepidic adenocarcinoma is the largest.Lepidic adenocarcinoma is larger than minimally invasive adenocarcinoma.Lepidic adenocarcinoma is larger than adenocarcinoma in situ.SUVmax values range from 1.25 to 15.93 with an average of 6.25.SUVmax of lepidic adenocarcinoma is approximately 4.2 times as SUVmax of minimally invasive adenocarcinoma and 5.8 times as that of adenocarcinoma in situ.(2)The mean value of minimally invasive adenocarcinoma was 1.482,and the mean value of adenocarcinoma in situ was 1.06,but there was no significant difference in the SUVmax values between the two groups.Third,SUVmax values in clinical T stages of early lung adenocarcinoma:Tis and Tib,Tis and T1c,T1a and T1c,T1b and T1c had significant difference.Tis and T1a,T1a and T1b had no significant difference.SUVmax value T1c>T1b>Tis,T1c>T1a.The distribution of SUVmax in various clinical T stages of early lung adenocarcinoma:(1)SUVmax of T1c is the largest,T1c is greater than T1b,and SUVmax of T1c is 1.9 times as T1b.SUVmax of Tis is the smallest with an average of 1.06,and the mean value of T1a was 2.27,and there was no significant difference between Tis and T1a.3 Analysis results of correlation among image analysis parameters,various pathological subtypes,PET/CT SUVmax and EGFR mutation.First,there is no correlation between generalized line reference number density of cancer cells in glands,nucleolus occurrence rate in glands,gland cell adhesion rate,the maximum distance between glands,the minimum distance between glands,nucleus morphological parameters(long axis,short axis,perimeter,area,roundness and regular form factor)and EGFR gene mutation.Second,gender is weakly associated with EGFR gene mutation,and smoking is negatively correlated with EGFR gene mutation.There was no correlation between tumor site,tumor diameter,pathological subtype,SUVmax and EGFR gene mutation.Third,the frequency of EGFR gene mutation in adenocarcinoma in situ is higher than that in lepidic adenocarcinoma,.Conclusion1.In the pathological classification of early lung adenocarcinoma,generalized line reference number density of cancer cells in glands,nucleolus occurrence rate in glands,gland cell adhesion rate,the maximum distance between glands,the minimum distance between glands and nucleus morphological parameters(long axis,short axis,perimeter,area,roundness and regular form factor)had application value in the quantitative analysis of early lung adenocarcinoma and can be used as quantitative parameter for differential diagnosis of early lung adenocarcinoma.2.In various clinical T stages of early lung adenocarcinoma,generalized line reference number density of cancer cells in glands,gland cell adhesion rate can be used as an important supplementary descriptive feature,which is helpful for clinicians to judge the prognosis of patients with early lung adenocarcinoma at different stages.3.The shape of the cell nucleus of various pathological subtypes and various T stages is relatively regular,relatively close to a circle or an ellipse,and the heterogeneity between the nucleus is not large.4.There was a moderate positive correlation between the nucleolus appearance rate,tnucleus short axis,nucleus circumference and SUVmax.There was a weak positive correlation between gland cell adhesion rate,nucleus long axis,nucleus area and SUVmax.There was a negative correlation between the maximum distance between glands and SUVmax.There was no correlation betweengeneralized line reference number density of cancer cells in glands,the minimum distance between glands,nucleus roundness and regular form factor and SUVmax.These results can help to deepen the understanding of tissue cell morphology and tissue structure of SUVmax under different degrees,and make further analysis and judgment on the properties of the grinding glass nodules.5.PET/CTSUVmax of early lung adenocarcinoma is of great value in the diagnosis of lepidicb adenocarcinoma and is difficult to diagnose adenocarcinoma in situ and minimally invasive adenocarcinoma.6.PET/CTSUVmax of T1b and T1c is of great value in the diagnosis of early lung adenocarcinoma but difficult at the stage of T1a and Tis.7.In early lung adenocarcinoma,there was no correlation between the size of the nucleus,the number and density of the nucleus,the nucleus shape,the number of nucleolus,the phenomenon of cell adhesion nucleolus,the width of the interstitial substance in the gland and the EGFR gene mutation,they are independent indicators.8.Female patients are more likely to have EGFR gene mutation than male patients,and non-smoking patients are more likely to have EGFR gene mutation than smoking patients.Whether women,smoking,and EGFR gene mutation are independent or interrelated,we need to explore.9.The EGFR gene mutation frequency in situ adenocarcinomais is higher than that of lepidicb adenocarcinom.The lepidic adenocarcinoma is probably not evolved from adenocarcinoma in situ or minimally invasive adenocarcinoma. |
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