| By using transrectal ultrasound (TRUS), prostate cancer (PCa) could be found out by certain signs, such as hypoechoic lesion, morphous (irregular, thorn-like), high grade in blood flow classification, increased peak velocity in systolic (Vs), high resistant index (RI). According to these sings, most prostate cancer can be diagnosed.Meanwhile, some other signs could also be detected in prostate cancer, such as echo halo marginal, micro-calcification and posterior acoustic attenuation. Those sings are of grate importance in thyroid and breast cancer diagnosis. Whether these signs are useful in diagnosis of prostate cancer is remain unclear.Because hypoechoic lesion and blood flow are important for prostate cancer diagnosis,it is important to study the hypoechoic lesion in prostate inner gland and the character of blood flow in normal prostate and prostate cancer.Changes in ultrasonic images were based on the changes of pathology, and such changes were also related to changes in molecular expression. But the relationship between these changes was indefinite.Once the relationship between ultrasound manifestation and molecular basis have been clarified, the micro molecular behavior could be judged by noninvasive ultrasound, and could provide a proof in prognosis of prostate cancer and predicting the process of prostate cancer. Similar researches have been in progress in radiation field, while the studies with ultrasound are rare.Objectives:After screening the ultrasonic manifestation which may be helpful to prostate cancer diagnosis and expression of proteins which related to tumor proliferation and differentiation, invasion and metastasis, blood vessel proliferation factors, we analyzed the relationship between those factors protein expression and ultrasonic manifestations to discuss the micro- biology basis of ultrasonic manifestation and to provide theoretical basis for predict prognosis noninvasively.Methods:1. screening the ultrasonic manifestation in prostate cancer(1) Ultrasonic features compared between prostate cancer and hyper- plasia of prostate:Patients who had undergone TRUS exam and TRUS guided biopsy proved to be prostate cancer and benign prostate hyperplasia (BPH) were selected from 2005 to 2009. 74 cases were PCa, and 51 cases were BPH. Retrospective analysis TRUS data in all cases, the differences between two groups were compared, including ultrasonic manifestation (hypoechoic), morphous (irregular, thorn-like), posterior acoustic attenuation, micro- calcification, blood flow classification, Vs, RI.(2) ultrasound manifestation of hypoechoic lesion in prostate inner cancer and BPH were compared18 hypoechoic lesion case in prostate inner cancer were selected from 74 PCa cases,31 hypoechoic lesion case in BPH were selected from 51 BPH cases, the differences between two groups were compared, including morphous (irregular, thorn-like), posterior acoustic attenuation, micro- calcification, Vs, RI.(3) the character of blood flow in normal prostate and prostate cancer.11 prostate outer gland cancer cases and 8 inner gland cancer cases were selected from above 74 PCa cases . 16 normal cases were selected from the patients who had undergone TRUS exam 2005 to 2009. Observed the starting time and the ending time of Transrectal contrast enhanced ultrasonography in the prostate inner gland(16 cases),the prostate outer gland(16 cases),the prostate inner gland cancer lesion(8 cases),and prostate outer gland cancer Lesion.(11 cases).2. The relationship between features of factors expression and clinical pathology in prostate cancer 74 cases were classified in groups. According to histodifferentiation, 23 cases were middle-well differentiated and 51 poorly differentiated. According to the Whitmore-Jewett clinical staging system, all cases were divided into A+B stage (40 cases) and C+D stage (34 cases). 51 BPH cases were include as comparison group. The TRUS guided biopsy tissue were collected and be made as dot matrix slices. Immunohistochemical characters of EGFR,k-ras ,Braf ,hMSH2 ,hMSH6 , MMP2, MMP9,VEGF and MVD expression and the their relationship with clinical pathology were studied.3. Relationship between utrasonic features and factorsWe summerize TRUS manifestations characters of 74 PCa, including echotexture, morphous (irregular, thorn-like), posterior acoustic attenuation, with or without micro-calcification, blood flow classification, Vs, RI, combined with expression characters of EGFR,k-ras, Braf, hMSH2, hMSH6, MMP2, MMP9, VEGF and MVD, to find out the relationship between the TRUS manifestation and expression of factors protein by statistical methods.Results:1. screening the ultrasonic manifestation in prostate cancer(1) Ultrasonic features compared between prostate cancer and hyperplasia of prostate:The percentage of hypoechoic lesion in prostate cancer and hyperplasia of prostate was 56.76% and 35.90% respectively (P<0.05), morphous of irregular and thorn-like in prostate cancer and hyperplasia of prostate was 85.14% and 15.38% respectively(p<0.05), micro-calcification was 39.19% and 10.26% respectively( p<0.05) , posterior acoustic attenuation was 41.89% and 12.82% respectively ( p<0.05 ) , Vs was 44.00±15.30 and19.42±1.61 respectively ( p<0.05 ) and RI was1.14±0.13 and 0.45±0.04respectively(p<0.05).(2) ultrasound manifestation of hypoechoic lesion in prostate inner cancer and BPH were compared.morphous of irregular and thorn-like in hypoechoic lesion in prostate inner cancer and BPH was 88.89% and 12.90% respectively(p<0.05), micro-calcification was 38.89% and 19.68% respectively ( p<0.05 ) , posterior acoustic attenuation was 44.44% and 16.13% respectively(p< 0.05), Vs was 55.50±3.67 and 17.32±4.65 respectively(p<0.05)and RI was 0.76±0.10 and 0.51±0.03 respectively(p<0.05). Flow grade was related significantly to prostate cancer and hyperplasia of prostate(r=-0.388,p<0.01) and the grade of prostate cancer were higher than hyperplasia of prostate. The percentage of echo halo marginal in prostate cancer and hyperplasia of prostate was 35.14% and 38.46% respectively(p>0.05).(3) the character of blood flow in normal prostate and prostate cancer. there was no significant difference between the starting time of the prostate inner gland(27.36±3.05s)and the prostate outer gland (25.13±2.54s),no significant difference between the starting time of the inner gland cancer lesion (14.72±1.81s) and the outer gland cancer lesion (16.32±1.98s) too. the ending time of the prostate inner gland ,the prostate outer gland , the inner gland cancer lesion and the outer gland cancer Lesion had no difference.2. The relationship between features of factors expression and clinical pathology in prostate cancer(1) Features of factors expression:EGFR positive expression in prostate cancer and hyperplasia of prostate was 59.46% and 10.26% respectively(P<0.05), Braf was 64.86% and 10.26% respectively( P<0.05) , hMSH2 was 55.41% and 23.08% respectively ( P<0.05 ) , hMSH6 was 72.97% and 15.38% respectively(P<0.05), MMP2 was 67.57% and 15.38% respectively(P<0.05), MMP9 was 67.57% and 15.38% respectively(P<0.05), VEGF was 70.27% and 12.82% respectively(P<0.05) and MVD was36.41±9.14 and 10.68±4.29 respectively(P<0.05).(2) Relationship of clinical pathology1) Relationship of ages:Percentage of EGFR positive expression in prostate cancer with age not older than 60 and older than 60 was 47.62% and 75.00% respectively(P<0.05), K-ras was 45.24% and 93.75% respectively(P<0.05). There was no significant difference between two age groups in Braf , hMSH2, hMSH6, MMP2, MMP9, VEGF and MVD expression(P>0.05).2) Relationship of histological differentiation:Percentage of Braf positive expression in middle-well differentiation and poor differentiation was 43.48% and 74.51% respectively(P<0.05), MMP2 was 47.83% and 76.47% respectively(P<0.05), MMP9 was 43.48% and 92.16% respectively ( P<0.05 ) , VEGF was 47.83% and 80.39% respectively ( P<0.05 ) and MVD was 29.70±6.30 and 39.43±8.63 respectively(P<0.05).There was no significant difference between two groups in positive expression of EGFR,K-ras,hMSH2,hMSH6(P>0.05).3) Relationship of clinical stages:Percentage of Braf positive expression in A+B stages and C+D stages was 42.50% and 91.18% respectively(P<0.05), VEGF was 50.00% and 94.12% respectively(P<0.05), MMP2 was 45.00% and 94.12% respectively(P<0.05), MMP9 was 45.00% and 94.12% respectively(P<0.05) and MVD was 32.98±8.57 and 40.44±8.20 respectively(P<0.05)。There was no significant difference between two groups in positive expression of EGFR, K-ras, hMSH2 and hMSH6(P>0.05)4) Relationship between EGFR, K-ras and BrafThere was a positive correlation between expression of K-ras and Braf ( r=0.272,p<0.05) , K-ras and EGFR (r=0.615,p<0.001) and EGFR was positively correlated with Braf significantly (r=0.269,p<0.05).5) Relationship between expression of MMP2, MMP9, VEGF and MVD.There was a positive correlation between expression of VEGF and MVD (r=0.436, p<0.001) , VEGF and MMP2 (r=0.468, p<0.001) , VEGF and MMP9 (r=0.534, p<0.001), MVD and MMP2 (r=0.445, p<0.001), MVD and MMP9 (r=0.570, p<0.001) and MMP2 and MMP9 (r=0.777, p<0.001) respectively.3. Relationship between utrasonic features and factors:(1) There were 9 cases of isoechogenicity, 42 cases of hypo- echogenicity, 5 cases of hyperechogenicity and 18 cases of mixed- echogenicity. The difference of echogenicity were related significantly to expression of VEGF(r=0.305, p=0.008), MMP2(r=0.325,p=0.005) and MMP9(r=0.340,p=0.003). The expression of these factors was of the highest in mixed echogenicity and lowest in isoechogenicity.(2) There were 11 cases without features in morphous (irregular and thorn-like) and 63 cases with these features. The features in morphous were related significantly to expression of MMP2(r=0.331, p=0.004), MMP9(r=0.283, p=0.015), VEGF(r=0.547, p<0.01) and MVD(r=0.279,p=0.016). The expression of these factors was higher in PCa with echo halo marginal than those of without.(3) There were 43 cases without posterior acoustic attenuation and 31 cases with posterior acoustic attenuation. The posterior acoustic attenuation was related to expression of MMP2 significantly (r=0.237, p=0.042), it expressed higher in prostate cancer with posterior acoustic attenuation.(4) There were 45 cases without micro-calcification and 29 cases with micro-calcification. The micro-calcification were related to expression of k-ras(r=0.398, p<0.01)and EGFR(r=0.268,p=0.021)significantly. Those expressed higher in prostate cancer with micro-calcification.(5) There were 16 cases of 0 grade, 38 cases of 1 grade, 16 cases of 2 grade and 4 cases of 3 grade in blood flow classification. The grade of flow classification in prostate cancer were related to expression of VEGF(r=0.432,p<0.01), Braf (r=0.284,p=0.014), MMP2(r=0.547,p<0.01), MMP9(r=0.833,p<0.01)and MVD(r=0.587,p<0.01),.(6) There were 43 cases with Vs not higher than 50 cm/s and 31 cases with Vs higer than 50 cm/s. The Vs were related to expression of VEGF(r=0.354,p=0.002), EGFR(r=0.231,p=0.035), MMP2(r=0.307,p=0.014)and MVD(r=0.508,p<0.01). With higher blood flow speed, the protein expression increased.(7) There was 32 cases with RI less than 0.8 and 42 cases with RI higher than 0.8. The RI were not related to expression of VEGF, Braf, k-ras, EGFR, MMP2, MMP9, hMSH2, hMSH6 and MVD.Conclusions1. There was a significant relationship between PCa echo features and MMP2, MMP9, VEGF positive expression. It can reflect the infiltration and metastasis ability of PCa, and its prognosis.2. The features in morphous (irregular and thorn-like) were related significantly to expression of MMP2, MMP9, VEGF and MVD. It can reflect the infiltration and metastasis ability of PCa and its prognosis.3. The posterior acoustic attenuation was related to expression of MMP2 significantly. It can reflect the infiltration and metastasis ability of PCa, and its prognosis.4. The micro-calcification was significantly related to the expression of k-ras and EGFR. It can reflect the proliferation and differentiation ability of PCa.5. There was a positive correlation between blood flow classification and Braf, MMP2, MMP9, VEGF protein expression and MVD. It mainly reflected the infiltration and metastasis ability, and prognosis.6. There was a significant relationship between Vs and EGFR, MMP2, VEGF protein expression and MVD. It can reflect the infiltration and metastasis ability, and prognosis.7. There was no significant relationship between RI and any of the factors protein expression. What can reflect the biological characters of PCa needs further study.
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