Study on some histopathological features and expression of some immunohistochemical markers in prostatic carcinoma

Nội dung text: Study on some histopathological features and expression of some immunohistochemical markers in prostatic carcinoma

1. Journal of military pharmaco-medicine n08-2017 STUDY ON SOME HISTOPATHOLOGICAL FEATURES AND EXPRESSION OF SOME IMMUNOHISTOCHEMICAL MARKERS IN PROSTATIC CARCINOMA Vi Thuat Thang*; Tran Ngoc Dung*; Nguyen Dinh Tao** Nguyen Ngoc Hung*; Tran Ngoc Anh** SUMMARY Objectives: To determine some histopathological features and evaluate the expression of some IHC markers in prostate carcinoma (Pca). Subjects and methods: Histopathological study was performed on 84 specimens by using hematoxylin and eosin (H.E) stained tissue sections. IHC study was performed on 33 specimens by using IHC stained tissue sections with PSA, CK34βE12, p63, CK7, CK5/6, actin monoclonal antibodies. Results: Prostatic adenocarcinoma accounted for 96.4% (acinar type was the most common) and urothelial carcinoma of the prostate accounted for 3.6%. Gleason scores 5 - 7 were the most common. Of the 84 patients, 60 (73.2%) had high grade prostatic intraepithelial neoplasia (HGPIN) associated adenocarcinoma. There were 39% of adenocarcinoma with perineural invasion and 53.7% of adenocarcinoma with mucinous secretions. IHC showed 31 cases (94%) of Pca which were positive for PSA and 2 cases (6%) of urothelial carcinoma of the prostate were negative for PSA. The lower Gleason grade was stronger positive for PSA was and vice versa. All the tumor cells were negative for 34βE12, p63, CK7, CK5/6 and actin. Conclusion: Our data indicate that most of Pca are prostatic adenocarcinoma and Gleason scores 5 - 7 are the most common scores. HGPIN is strongly associated with adenocarcinoma. Other features are commonly seen in prostatic adenocarcinoma which are blue-tinged mucinous secretions and perineural invasion. IHC shows all of prostatic adenocarcinomas are positive for PSA, urothelial carcinoma of the prostate is negative for PSA. The staining intensity of the tumor cells for PSA is stronger in the lower grade adenocarcinomas and vice versa. * Keywords: Adenocarcinoma of the prostate; Immunohistochemistry. INTRODUCTION difficult to identify as being of prostatic Prostatic carcinoma is one of the origin [8]. Currently in about two-thirds of malignant tumours and often found in these difficult cases, an appropriate men over the age of 65. Nowadays, this diagnosis can be made due to IHC stains kind of tumour has the tendency to increase with the use of antibodies [4]. In Vietnam, dramatically in almost every country the studies on histopathological features around the world. Histopathologically, and the expression of IHC markers in adenocarcinomas of the prostate range carcinoma of the prostate are not adequate from well-differentiated gland forming to the demand [1]. The aim of this study is: cancers, where it is often difficult to To determine some histopathological distinguish them from benign prostatic features and evaluate the expression of glands, to poorly differentiate tumours, some IHC markers in Pca. * 103 Military Hospital ** Vietnam Military Medical University Corresponding author: Vi Thuat Thang (vithuatthang@yahoo.com) Date received: 23/03/2017 Date accepted: 27/09/2017 222
2. Journal of military pharmaco-medicine n08-2017 SUBJECTS AND METHODS Tissue sections of 33 cases were IHC stained with use of PSA, CK5/6, 1. Subjects. CK34βE12, p63 and actin monoclonal Eighty four consecutive prostate glands antibodies, in which there were 31 cases of operated by using transurethral resection adenocarcinoma and 2 cases of urothelial of the prostate (TURP) at Urology of carcinoma of the prostate. 103 Military Hospital from June, 2008 to - Determine the ratio of prostatic July, 2017. carcinomas which were positive for PSA, 2. Methods. CK34βE12, p63, CK7, CK5/6 and actin. - Distribute staining intensity of tumor Specimens were fixed in 10% neutral cells for PSA according to Gleason grade. buffered formalin, embeded in paraffin and cut on the microtoma. Tissue RESULTS AND DISCUSSION sections were stained with H.E and IHC 1. Distribution of patients’ age. stained with the use of PSA, CK5/6, Table 1: Distributed results of Pca among CK34βE12, p63, CK7, actin monoclonal age group (n = 84). antibodies. The results were presented and discussed. Age group No. of patients Ratio (%) (n = 84) * Distribution the age: Ages of patients were divided into 40 - 49 1 1.19 5 groups with the gap of 10 years 50 - 59 4 4.76 (< 50, 50 - 59, 60 - 69, 70 - 79 and ≥ 80). 60 - 69 20 23.81 * Study on histopathology: - Determine the types of histopathology 70 - 79 36 42.86 of the Pca according to the 2004 WHO ≥ 80 23 27.38 histological classification of tumours of the Total 84 100% prostate. - Evaluate the association between This table showed the incidence of Pca adenocarcinoma and HGPIN. increased with age group. The 70 - 79 - Grade the adenocarcinomas according age group was the highest with 42.86%, to the Gleason grading system. the 40 - 49 age group was the lowest with 1.19%. These results showed that - Group Gleason scores into diffentiation prostatic carcinoma was rarely found in categories. men below the age of 50 [1, 6, 8]. Our - Determine some histopathological results of distributed Pca among age features of prostatic adenocarcinoma. group are the same as the outcome of * Study on the expression of some IHC study carried out by Nguyen Van Hung [1], markers in prostatic carcinoma: Nguyen Buu Trieu [2] and others [7]. 223
3. Journal of military pharmaco-medicine n08-2017 2. Study on histopathology. HGPIN was a predictive factor which was Table 2: Determination of types of valuable in the diagnosis of adenocarcinoma histopathology of the Pca according to the of the prostate, especially HGPIN with 2004 WHO histological classification adjacent atypical glands (PINATYP) [8]. (n = 84). HGPIN in needle biopsy tissue was a risky factor for the subsequent carcinoma Types of histopathology No. of Ratio detection after re-biopsy [1, 2, 5, 9]. patients (%) Adenocarcinoma 82 96.4 Table 3: Grouping Gleason score into Acinar adenocarcinoma 80 97.6 diffentiation categories (n = 82). Dductal adenocarcinoma 2 2.4 Differentiated Gleason No. of Ratio Urothelial carcinoma 2 3.6 grade score patients (%) Squamous carcinoma 0 Well differentiated 2 - 4 14 17.1 Basal cell carcinoma 0 Moderately 5 - 7 58 70.7 differentiated Total 84 100% Poorly 8 - 10 10 12.2 This table showed adenocarcinoma differentiated accounted for 96.4% (in which acinar Total 82 100% adenocarcinoma was 97.6%, ductal Two cases of urothelial carcinoma of adenocarcinoma was 2.4%) and urothelial the prostate were not included in this carcinoma of the prostate accounted for scoring system. Gleason score tumors 3.6%. These results were the same as the 5 - 7 were the highest ratio (70.7%), Gleason results found by Nguyen Van Hung [1] score tumors 2 - 4 and 8 - 10 were 17.1% and others. and 12.2%, respectively. These results Table 3: Association between were the same as the study carried out by adenocarcinoma and HGPIN (n = 82). Nguyen Van Hung [1], Bostwick, Oesterling, Zincke [1, 3, 5, 10]. Histopathology No. of Ratio patients (%) Table 5: Distributed ratio of adenocarcinomas Adenocarcinoma is 60 73.2 according to malignant specific features associated with HGPIN 22 26.8 (n = 82). Adenocarcinoma is not associated with HGPIN Malignant specific Number Ratio Total 82 100 % features (%) Perineural invasion 32 39% Adenocarcinoma associated with HGPIN and accounted for 73.2%, Mucinous fibroplasia 9 11% much higher than adenocarcinoma, Glorumerulation 10 12.2% did not associate with HGPIN (26.8%). 2 or 3 of malignant specific 6 7.3% Nguyen Van Hung [1] also found that features 76.2% of prostatic carcinoma contained No malignant specific 25 30.5% features HGPIN. Clinical significance of HGPIN showed strong association with Pca [5]. Total 82 100% 224
4. Journal of military pharmaco-medicine n08-2017 The table showed adenocarcinoma crystalloids and mucinous secretions (22%), with perineural invasion was found in no crystalloids and mucinous secretions 39% of cases, adenocarcinoma with (14.6%). glorumeration and mucinous fibroplasia Crystalloids, despite not diagnostic of were found in 12.2% and 11%, respectively. carcinoma, were more frequently found in Adenocarcinoma with 2 or 3 malignant low grade cancer than in benign glands specific features were found in 7.3% of [11]. Young [9] also showed that the cases while adenocarcinoma with no incidence of crystalloids in the adenocarcinoma malignant specific features were found in ranged 10 - 62%. Blue-tinged mucinous 30.5% of cases. There were only 3 secretions seen in H.E stained sections features that are in and of themselves were additional finding seen preferentially diagnostic of cancer. These were perineural in cancer, especially low grade cancer [8]. invasion, mucinous fibroplasia and glorumeration. Perineural invasion specimens by prostate cancers were seen in radical prostatectomy specimens in 75 - 84% of cases. Most studies indicate that its pesesence corellated with extraprostatic extension (38 - 93%). Recent data suggest that this finding may indipendently predict lymph-node metastasis and prognosis after surgery [8]. Fig.1: Well- differentiated adenocarcinoma, Gleason grade 2. Table 6: Distributed ratio of adenocarcinoma (Arrow: mucinous secretions) according to intraluminal features (n = 82). (No. S2835 x 200.HE) Intraluminal features Number Ratio (%) Crystalloids 8 9.7% Blue-tinged mucinous 44 53.7% secretions Crystalloids and 18 22% mucinous secretions No crystalloids and 12 14.6% mucinous secretions Total 82 100% Fig.2: Poorly differentiated adenocarcinoma, Gleason grade 4. Crystalloids were found in 9.7% of cases, (Arrow: perineural invasion) blue-tinged mucinous secretions (53.7%), (No.S3475 x 400.HE). 225
5. Journal of military pharmaco-medicine n08-2017 3. Study on immunohistochemistry. Table 7: Ratio of Pca which were positive for PSA, 34βE12, p63, CK7, CK5/6 and actin (n = 33). Type of marker Number of positive cases Ratio (%） PSA 31/33 94% 34βE12 0/33 0% p63 0/33 0% CK7 0/33 0% CK5/6 0/33 0% Actin 0/33 0% The study results were consistent with the findings of other studies [1, 4, 8]. Table 8: Staining intensity distribution of tumor cells with PSA according to Gleason grade (n = 31). Intensity Number Grade 2 Grade 3 Grade 4 Grade 5 (1+) 7 5 2 (2+) 15 15 (3+) 9 9 (4+) 0 Tổng 31 9 15 5 2 (Positive: +; Faint: 1+; Moderate: 2+; Strong: 3+; Very strong: 4+) IHC showed tumor cells which were strong positive for PSA in the areas of Gleason grade 2, moderate positive for PSA in the areas of Gleason grade 3, faint positive for PSA in the areas of Gleason grade 4 and 5. The study results were consistent with the findings of other studies. The finding is that the more the differentiated tumor cell is, the stronger the positive intensity for PSA is and vice versa [1, 4, 8]. Fig 3: Gleason grade 2. Fig 4: Gleason grade 3. Fig 5: Gleason grade 4. (Arrow: strong positive) (Arrow: moderate positive) (Arrow: basal cells (2+) for No. N3351 x200. PSA. No. N3351 x200. PSA 34βE12 in benign glands) (No. N2519 x200. 34βE12). 226
6. Journal of military pharmaco-medicine n08-2017 CONCLUSION tuyến tiền liệt ở giai đoạn muộn. Chẩn đoán và điều trị. Tạp chí Ngoại khoa. 1991, 1, tr.9-13. * Histopathological features: 3. Bostwick D.G. Prostatic intraepithelial Prostate carcinoma is common in the neoplasia. Urol (suppl). 1999, 34 (6), pp.23-27. older men. Most of Pca are adenocarcinoma 4. Buchwalow I.B, W. Böcker. in which acinar adenocarcinoma type is the Immunohistochemistry: basics and methods. most common, ductal adenocacinoma is a Springer Science & Business Media. 2010. rare variant of prostatic adenocarcinoma. 5. Oesterling J.E, Brendler C.B, Epstein J.I Gleason scores 5 - 7 are the most common. et al. Correlation of clinical stage, serum Adenocarcinoma is strongly associated prostatic acid phosphatase and preoperative Gleason grade with final pathological stage in with HGPIN. Other features commonly 275 patients with clinically localized prostate seen in prostatic adenocarcinoma which cancer. J Urol. 1987, 138, pp.92-96. are blue-tinged mucinous secretion and 6. Stanley L.Rbbins M.D. Pathologic basis perineural invasion. of disease. W.B. Saunders Company. 1974, * Expression of some immunohistochemical pp.1190-1198. markers: 7. Tannenbaurn M, Galang C.F, Park C.H et al. Dysplasia of the prostate, a precursor IHC shows all of prostatic adenocarcinomas lesion of prostatic cancer. Ann Urol. 1991, are positive for PSA, urothelial carcinomas pp.27-49. of the prostate are negative for PSA. The 8. John N. Eble, Guido Sauter, Jonathan I. staining intensity of the tumor cells for Estain, Isabell A. Sesterhenn. Pathology and PSA are stronger in the lower grade genetics of tumours of the urinary system and adenocarcinomas and vice versa. Tumor male genital organs. IARCPress. Lyon. 2004, cells are negative for CK34βE12, p63, chapter 3, pp.159-215. CK7, CK5/6 and actin. 9. Young R.H, Srigley J.R, Amin M.B, Ulbright T.M, Cubillia A.L. Tumors of the REFERENCES prostate gland, seminal vesicles, male urethra, and penis. 3rd, Fascicle 28. Raven. 2000, 1. Nguyễn Văn Hưng. Nghiên cứu mô pp.1-344. bệnh học quá sản lành tính, tân sản nội biểu 10. Zincke H, Farrow G.M, Myers R.P et al. mô và ung thư biểu mô tuyến tiền liệt. Luận Relationship between grade and stage of án Tiến sỹ Y học. 2005. adenocarcinoma of the prostate and regional 2. Nguyễn Bửu Triều, Nguyễn Kỳ, Trần pelvic lymph node metastases. J Urol. 1982, Đức Thọ. Các biểu hiện lâm sàng của ung thư 128, pp.498-501. 227