子宫内膜上皮内肿瘤形态学诊断及PTEN蛋白表达情况

目的 探讨子宫内膜上皮内肿瘤(EIN)病理诊断标准及PTEN在子宫内膜病变中的表达情况.方法 收集子宫内膜病变51例,按照EIN诊断标准复习切片重新诊断并与原诊断进行比较.同时做免疫组织化学PTEN(EnVision方法)染色,观察其表达情况.结果 经重新诊断,2例原诊断单纯增生者有小灶EIN存在,3例原诊断不典型增生者不足EIN标准.增殖期子宫内膜、良性增生、EIN、子宫内膜样癌PTEN缺失率分别为50.0%(4/8)、50.0%(4/8)、66.7%(16/24)及81.8%(9/11).各组缺失率差异无统计学意义(P=0.383).结论 EIN组织学诊断标准是可行的,但与传统应用的子宫内膜增生分类有一定的差别.PTEN缺失在诊断中有提示作用,但不能作为确定诊断的依据.     

The endometrial hyperplasias revisited

The proliferating lesions in the endometrium form a morphological continuum extending from benign to malignant, through a transitional pre-invasive stage. Within this spectrum, several classifications of endometrial hyperplasia have been developed over the years in which the precancerous lesions gained a substantial distinction, although not without inconsistencies in definitions and terminology. The revised WHO 1994 classification explicitly recognizes cytological atypia as the defining feature for distinguishing genuine hyperplastic lesions (simple and complex endometrial hyperplasia) from those that are potentially precancerous (simple and complex atypical endometrial hyperplasia) and puts an end to the verbal anarchy by adopting a common language of communication. This taxonomy, however, was criticized for complexity and low level of reproducibility. Thus, in the name of improved reproducibility a new classification was recently proposed which (a) combines simple and complex endometrial hyperplasia within one diagnostic category known as endometrial hyperplasia and (b) defines new criteria for recognising the precancerous lesions: a monoclonal growth, known as endometrial intraepithelial neoplasia (EIN), comprising clusters of crowded glands, greater than 1 mm in diameter, having a cytologically altered epithelium. The EIN concept was challenged of not being independently tested and received with great enthusiasm by some scholars and relative skepticism by others.     

Yield of annual endometrial cancer surveillance in women with PTEN Hamartoma Tumor Syndrome

ObjectiveExpert-opinion based guidelines state that endometrial cancer surveillance (ECS) might be considered for patients with PTEN Hamartoma Tumor Syndrome (PHTS) based on an elevated lifetime risk of endometrial cancer. We aimed to evaluate the yield of ECS by annual transvaginal ultrasound (TVUS) and endometrial biopsy (EMB) in PHTS patients.MethodsPHTS patients who visited our PHTS expert center between August 2012 and September 2020 and opted for annual ECS were included. Data on surveillance visits, diagnostics, reports of abnormal uterine bleeding and pathology results were retrospectively gathered and analyzed.ResultsSurveillance was initiated in 25 women with a total of 93 gynecological surveillance visits during 76 surveillance years. The median age at first visit was 39 years (range 31–60) with a median follow-up duration of 38 months (range 6–96). Hyperplasia with and without atypia was detected six and three times, respectively, in seven (28%) women. The median age at hyperplasia detection was 40 years (range 31–50). In six asymptomatic women hyperplasia was detected during annual surveillance visits, while in one patient hyperplasia with atypia was detected during an additional visit due to abnormal uterine bleeding. In seven out of nine hyperplasias detected with EMB, TVUS beforehand showed no abnormalities. No (interval) carcinomas occurred.ConclusionsECS in women with PHTS enables detection of a substantial number of asymptomatic premalignancies, such as hyperplasia with and without atypia, suggesting that ECS may be beneficial with regard to cancer prevention. The addition of EMB to TVUS likely improves the detection of premalignancies.     

Immunohistochemical expression of PTEN and beta-catenin for endometrial intraepithelial neoplasia in Japanese women

PTEN and beta-catenin are the most common genes for which genetic abnormalities are found in endometrioid adenocarcinoma (type I) and even in their precursors. Currently, the World Health Organization (WHO) classifies endometrial hyperplasia as a premalignant disease. However, one of the problems in the current WHO endometrial hyperplasia schema is that it is not always a reproducible classification system. Subsequently, the alternative molecular genetics and morphometric-based classification, referred to as the endometrial intraepithelial neoplasia (EIN) classification system, has been proposed. We reclassified endometrial lesions in Japanese women using the EIN category and compared them with the results of PTEN as well as beta-catenin immunohistochemistry. A total of 117 cases that were initially diagnosed as endometrial hyperplasia according to WHO classification were reevaluated histopathologically by the EIN diagnosis category. They were classified into 38 EIN and 32 benign architectural changes of unopposed estrogen (BAC), and 47 cases were excluded. In addition, for comparison, we examined 20 cases of normal proliferative endometrium (NPE). Subsequently, the expressions of PTEN and beta-catenin were analyzed immunohistochemically. Glandular epithelium was positive for PTEN in all the cases of NPE (20/20), whereas 12.5% (4/32) of BAC and 34.2% (13/38) of EIN were PTEN-null (negative). Endometrial intraepithelial neoplasia was significantly less frequently positive for PTEN than NPE (P < .025). The nuclear staining for beta-catenin was seen in 26.3% (10/38) of EIN cases, and the intensity was generally strong. Instead, none of the BAC or NPE showed positive nuclear staining. Thus, the nuclear staining was statistically more frequently seen in EIN than in the other 2 categories (P < .025 for each). In addition, 22 of 38 EIN cases (57.9%) were either PTEN-negative or nuclear beta-catenin-positive. This combination was statistically significantly more frequently seen than BAC (4/32, 12.5%) (P < .001) and NPE (0/20, 0%) (P < .0001). Immunohistochemical loss of PTEN and positive nuclear staining of beta-catenin were frequently seen in EIN but were not seen in NPE cases in Japanese women. The combination of PTEN-negative/beta-catenin-positive results may become the reliable marker for detecting EIN.     

子宫内膜增生及内膜癌中PTEN、Ki-67蛋白的表达

目的　研究子宫内膜增生组织及内膜癌组织中PTEN、Ki 6 7蛋白的异常表达 ,探讨其与子宫内膜癌变的关系及作为早期癌变生物学标志的可能性。方法　应用免疫组化S P法对 12例正常增生期子宫内膜组织、4 0例子宫内膜增殖症组织、4 2例内膜腺癌组织中PTEN、Ki 6 7蛋白的表达进行研究。结果　在正常增生期子宫内膜、子宫内膜增殖症 (单纯增生、复杂型增生、不典型增生 )、子宫内膜腺癌组织中PTEN蛋白的阳性表达率呈递减趋势 ;Ki 6 7蛋白的阳性表达率呈递增趋势。等级相关分析结果显示PTEN、Ki 6 7表达异常与子宫内膜组织学分级均显著相关 (相关系数r分别为 - 0 5 4 1和 0 4 96 ,P值均<0 0 1)。子宫内膜癌与除不典型增生外的子宫内膜增殖症组织及正常增生期子宫内膜组织的PTEN、Ki 6 7蛋白表达差异有显著性 ,正常增生期子宫内膜、单纯增生与不典型增生组织的PTEN蛋白表达差异有显著性 ,不典型增生与单纯增生组织的Ki 6 7蛋白表达差异有显著性。PTEN、Ki 6 7蛋白表达存在负相关性 (r =- 0 4 2 8,P <0 0 1)。PTEN、Ki 6 7蛋白的表达与子宫内膜癌的手术分期、组织学分级、肌层浸润无关 (P >0 0 5 )。结论　PTEN、Ki 6 7蛋白的异常表达与子宫内膜的癌变过程相关 ,PTEN基因表达异常及细胞增殖异常与子宫内膜     

Alteration of PTEN expression in endometrial carcinoma is associated with down-regulation of cyclin-dependent kinase inhibitor,p27

AIMS: PTEN is a recently identified tumour suppressor inactivated in a wide variety of human cancers, including endometrial cancers. Mutation of the PTEN tumour suppressor gene has been reported in approximately 50-83% of endometrial adenocarcinoma. Despite this fact, study of the expression of PTEN protein in human tumours is limited. PTEN protein functions as a tumour suppressor by regulating the cell cycle and survival through signal transduction pathway. PTEN protein was considered to have a dual-specificity phosphatase activity, but it is now known that its principal physiological activity is mainly derived from its lipid phosphatase activity. The cyclin-dependent kinase inhibitor, p27, has been suggested as a downstream target of cell cycle arrest of PTEN in various in vitro studies. In this study, we evaluated the alteration of PTEN protein expression in endometrial carcinoma and assessed its relationship to the expression of p27, the presumed downstream target of PTEN. METHODS AND RESULTS: Immunohistochemical staining was performed on 66 cases of endometrial carcinoma including 61 endometrioid type and five serous type, using antibodies to PTEN and p27. Loss or decrease of PTEN expression was observed in 66% (40/61 cases) of uterine endometrioid carcinoma, whereas most uterine serous carcinoma (4/5 cases) showed intense PTEN expression. Four (30%) of 13 endometrial hyperplasia synchronous with endometrioid carcinoma demonstrated complete loss of PTEN expression. All endometrioid carcinoma synchronous with PTEN-negative endometrial hyperplasia showed loss of PTEN expression. Alteration of PTEN expression was not correlated with histological grade or stage. Decreased immunoreactivity of p27 was found in 48 cases (79%) of 61 endometrioid carcinoma, and 76% (36 cases) of them also showed loss or decrease of PTEN expression. Four of five uterine serous carcinoma revealed strong p27 immunoreactivity, all of which showed intense PTEN expression. A positive correlation between PTEN and p27 expression was statistically significant (Mantel-Haenszel chi2 test, P=0.001). Immunoreactivity of p27 was not related to histological grade and clinical stage. CONCLUSION: These results show that PTEN and p27 are differentially expressed in endometrioid type carcinoma compared with those of the serous type, and suggest that the cyclin-dependent kinase inhibitor, p27, is a downstream target of PTEN-dependent cell cycle arrest in endometrial carcinoma.     

Endometrial hyperplasia and the risk of progression to carcinoma

The primary presenting symptom of endometrial neoplasia is abnormal uterine bleeding, which typically prompts an endometrial biopsy to rule out carcinoma. Approximately 70% of women with abnormal uterine bleeding are diagnosed with benign findings and 15% are diagnosed with carcinoma. The remaining 15% receive a diagnosis of endometrial hyperplasia (EH), which includes a broad range of lesions, from mild, reversible proliferations to the immediate precursors of carcinoma. The widely used World Health Organization (WHO) system classifies EH according to four combinations of glandular crowding and nuclear atypia: simple (SH), complex (CH), simple atypical (SAH), or complex atypical hyperplasia (CAH), although the two forms of atypical hyperplasia (AH) are often collapsed into one category. Diagnoses of EH raise three issues. First, the low interobserver reproducibility—less than 50% in almost all studies—hinders the ability of WHO-based classification to effectively guide clinical management. Second, approximately 50% of women diagnosed with AH have concurrent carcinoma. Not surprisingly, most women with AH undergo hysterectomy as primary treatment, but non-surgical management can be effective. Third, data on progression risks for women with EH who retain their uterus are extremely limited. Emerging data indicate the long-term risk among women with SH or CH is less than 5%, but the risk among women with AH is approximately 30%. These data highlight priority areas for future research, such as increasing the diagnostic reproducibility of EH, improving the discrimination between AH and carcinoma, and identifying biomarkers to stratify risks or serve as indicators of response to clinical treatment.     

Occludin expression decreases with the progression of human endometrial carcinoma

The tight junctions of the glandular epithelium are crucial for the maintenance of cell polarity, separating the plasma membrane into apical and basolateral domains. Thus abnormalities of the tight junctions may result in the structural disturbances of glandular epithelial neoplasia. In this study we introduced an anti-occludin monoclonal antibody for semiquantitative assay of the occludin expression in tissue sections of human normal and neoplastic endometrial epithelia using the Adobe Photoshop and NIH Image programs. Normal endometrial glands and samples of endometrial hyperplasia and endometrioid carcinoma grade 1 fully expressed occludin at the apical cell border. In endometrioid carcinomas grades 2 and 3, however, occludin disappeared in solid areas of the carcinomatous tissues. Occludin was also found at the apical borders of the cancer cells that formed glandular structures. Occludin expression decreased progressively in parallel with the increase in carcinoma grade, and the decreased occludin expression correlated with myometrial invasion and lymph node metastasis. These results suggest that the loss of tight junctions has a close relationship with structural atypia in the progression of human endometrial carcinomas and their malignant potential.     

Downregulation of GLTSCR2 expression is correlated with breast cancer progression

Glioma tumor-suppressor candidate region gene2 (GLTSCR2) is a recently identified nucleolus-localized protein participating in the regulation of cell cycle progression and apoptosis. Down-regulation of GLTSCR2 in several types of cancers and increased transforming activity in GLTSCR2-downregulated cancer cells indicated its tumor suppressive potential. The aim of this study was to evaluate GLTSCR2 expression in breast cancer and to investigate the question of whether reduced expression of GLTSCR2 may have any pathological significance in breast cancer development or progression. In this study, we performed quantitative RT-PCR and immunohistochemistry to evaluate the expression of GLTSCR2 and relevance with clinicopathological factors in the invasive ductal carcinoma (IDC). GLTSCR2 expression was reduced in 48% of IDC (n = 426) by a semi-quantitative scoring system using tissue microarray. GLTSCR2 mRNA was significantly reduced by 0.16 fold in 15 out of 17 (88%) cases of IDC. Reduction of GLTSCR2 was significantly correlated with increased histological grade (p < 0.005), increased tumor size (p < 0.001), axillary lymph node involvement (p < 0.001) and decreased disease free survival (p < 0.025). In addition, we show that upregulation of GLTSCR2 decreases the invasive potential of breast cancer cells. Taken together, our data suggest that GLTCR2 may play a role in the tumorigenesis, progression and biological behavior in breast cancer.     

宫颈腺癌和腺上皮内肿瘤组织中PTEN基因的突变和蛋白表达

目的 探讨PTEN基因的突变和表达在宫颈腺癌发生中的作用.方法 应用免疫组织化学SP法检测42例宫颈腺癌、20例宫颈腺上皮内肿瘤和28例正常宫颈组织中PTEN蛋白表达,并采用聚合酶链反应-单链构象多态性(PCR-SSCP)法检测上述组织中PTEN基因第5、8外显子突变情况.结果 宫颈腺癌、宫颈腺上皮内肿瘤和正常宫颈腺上皮组织中PTEN蛋白的阳性表达率分别为54.8%(23/42)、25.0%(5/20)和100%(28/28),其差异均有统计学意义(P<0.05);黏液型和子宫内膜型宫颈腺癌组织中PTEN蛋白阳性表达率分别为9/19和2/10,其他组织学变型PTEN蛋白阳性表达率92.3%(12/13).宫颈腺癌、宫颈腺上皮内肿瘤和正常宫颈组织中PTEN基因第5、8外显子的突变率分别为19.0%(8/42)、45.0%(9/20)和0,其差异均有统计学意义(x<,2>=4.29,x2=12.70;均P<0.05);黏液型和子宫内膜型宫颈腺癌PTEN基因第5、8外显子的突变率分别为4/19和4/10,其他组织学变型未检测到突变.结论 宫颈腺癌的发生与PTEN基因的突变和蛋白表达产物缺失有关,PTEN基因的突变和蛋白表达产物缺失可能是宫颈腺癌发生中的早期事件.     

Reduced expression of PTEN correlates with breast cancer progression

PTEN is a tumor-suppressor gene with phosphatase activity that is mutated in a variety of cancers. We analyzed a series of 34 invasive and 18 in situ breast cancers with known molecular status of the PTEN genotype using immunohistochemistry. Reduced PTEN protein expression was seen in 38% of invasive cancers and in 11% of in situ cancers. The frequency of reduced expression was highest in stage II and III cancers. Reduced expression also correlated with aneuploidy. In addition, in tumors with both in situ and invasive components, expression within the ductal carcinoma in situ portion tended to reflect the expression pattern of the invasive component. These data suggest that PTEN expression is frequently reduced in advanced breast cancers.     

前列腺癌PTEN表达的丢失与病理分级、分期关系

目的 探讨前列腺癌组织中抑癌基因PTEN蛋白的表达丢失情况及临床病理意义。方法 应用免疫组化SP法检测了38例前列腺癌及其相应的癌旁组织中PTEN蛋白的表达情况，同时结合肿瘤病理分级及分期进行分析。结果 阳性信号定位于上皮细胞胞质中，呈棕色颗粒状物，所有良性前列腺上皮均阳性着色。所有肿瘤细胞均出现颗粒状胞质着色为阳性组，瘤细胞阳性与阴性共存为混合组，肿瘤组织完全不着色为阴性。其中阳性4例(10．52％)，混合27例(71．05％)，阴性7例(18．42％)。PTEN表达的丢失与Gleason分级相关且与高分级(Ⅳ、Ⅴ级)及高分期(进展期癌T3b、T4)相关。结论 前列腺癌的进展中PTEN基因失活可能起重要作用，PTEN表达的丢失可能与前列腺癌的不良预后有关。     

The use and disuse of morphometry in the diagnosis of endometrial hyperplasia and carcinoma

Endometrial adenomatous hyperplasia, and the different grades of endometrial carcinoma form a continuous spectrum of morphologic deviations. The reproducibility and consistency of the assessment of these microscopical patterns is a historical problem ("nicht Karzinom - aber besser hinaus"). Lack of objective criteria is the major cause of this. Computer-aided morphometric analysis has revealed the diagnostic significance of several quantitative microscopical features. Using these in a multivariate combination, a highly reproducible and objective classifier has been developed. Selection of the significant areas by skilled gynaecopathologists is essential for the useful application of this algorythm. Especially in cases of doubt, this classification rule can be of decisive importance. Routine application in diagnostic gynaecopathology of this selective type of morphometry over a period of four years has regularly corrected the original subjective histopathological grade. In a case of a young patient with an unsuspected sexcord tumor of the ovary with annular tubules, the erroneous diagnosis of endometrial carcinoma was corrected by the application of morphometry into adenomatous hyperplasia. An excision of the ovarian tumor was performed, and slowly the morphologic pattern of the subsequent microcurettings revealed a more and more normal microscopical pattern, with eventually signs of secretion. Other studies have shown, that morphometrical analysis of adenomatous hyperplasias can predict the majority of those patients, who will develop frank carcinoma in their later course. Finally, objective histopathological grading of carcinomas reveals the superior quality of morphometry above subjective qualitative methods. Prevention of under- or overtreatment with radiotherapy can therefore be the result of routine diagnostic morphometry.(ABSTRACT TRUNCATED AT 250 WORDS)     

P16<Superscript>INK4a</Superscript> expression and progression risk of low-grade intraepithelial neoplasia of the cervix uteri

The aim of the study was to evaluate the immunohistochemical expression of p16^INK4a as a marker of progression risk in low-grade dysplastic lesions of the cervix uteri. p16^INK4a immunohistochemistry was performed on 32 CIN1 with proven spontaneous regression of the lesion in the follow-up (group A), 31 (group B) with progression to CIN3 and 33 (group C) that were randomly chosen irrespective of the natural history of the lesion. p16^INK4a staining pattern was scored as negative (less than 5% cells in the lower third of dysplastic epithelium stained), as focally positive (25%) and as diffuse positive (>25%). A diffuse staining pattern was detected in 43.8% of CIN1 of group A, 74.2% of group B and 56.3% of group C. No p16^INK4a staining was detected in 31.3% and 12.9% CIN1 lesions of groups A and B, respectively. Overall, 71.4% and 37.8% of p16^INK4a-negative and diffusely positive CIN1 had regressed at follow-up, whereas 28.6% and 62.2% negative and diffusely positive CIN1 were progressed to CIN3, respectively (P<0.05). All CIN3 lesions analyzed during follow-up of group B were diffusely stained for p16^INK4a. Although p16^INK4a may be expressed in low-grade squamous lesions that undergo spontaneous regression, in this study, CIN1 cases with diffuse p16^INK4a staining had a significantly higher tendency to progress to a high-grade lesion than p16^INK4a-negative cases. p16^INK4a may have the potential to support the interpretation of low-grade dysplastic lesions of the cervix uteri.     

Prediction of coexistent carcinomas risks by subjective EIN diagnosis and comparison with WHO classification in endometrial hyperplasias

Endometrial intraepithelial neoplasia (EIN) classification is proposed as a new diagnostic system to resolve the limitations of the World Health Organization (WHO) classification in routine practice. Our aim was to find out whether EIN classification excels the WHO classification regarding the accurate prediction of coexisting endometrial carcinomas (EC) in biopsy specimens.     

Cytologic criteria of hyperplastic lesions in endometrial samples obtained by the endocyte sampler

The present investigation attempted to identify useful parameters for the cytologic diagnosis of endometrial hyperplasias in samples obtained with the Endopap endometrial sampler. A clinical and morphological classification dividing hyperplasia into benign simple hyperplasia (BSH); benign complex hyperplasia (BCH); and endometrial intraepithelial neoplasia (EIN) has been suggested by Meisels, et al. based on five valuable cytologic criteria. To these we added six of our own and applied them to 1.172 cases, 432 of which had a previous histologic diagnosis of normal proliferative endometrium (NPE); 462 were BSH, 210 were BCH, and 14 fit the EIN pattern. The cytologic criteria evaluated were overlapping cells, enlarged nuclei, aniso karyosis, granularity of chromatin, stromal cells, branching glandular structures, and moruloid or papillary-like cellular aggregates, dilated glandular borders in cellular sheets, nuclear clearing, clumped chromatin, and enlarged eosinophilic cytoplasm. Our results are consistent with the following findings: (1) there is no useful parameter for cytologic differentiation between NPE and BSH; (2) BCH is characterized by cellular aggregates, dilated glandular borders in cellular sheets, and branching glandular structures; (3) EIN is characterized by nuclear clearing, clumped chromatin, and anisokaryosis; and (4) enlargement of nucleoli and eosinophilic cytoplasm alone is not sufficient for the diagnosis of EIN.     

Overexpression of EZH2 and loss of expression of PTEN is associated with invasion, metastasis, and poor progression of gallbladder adenocarcinoma

Overexpression of EZH2 and inactivation or loss of PTEN expression was observed in invasive and metastatic tumors. However, their expressions and clinical significances in gallbladder cancer (GBC) have rarely been reported. In this study, we investigated EZH2 and PTEN expression in an extensive collection of human gallbladder cancer samples and benign lesions of gallbladder using immunohistochemistry. Overexpression of EZH2 was detected in 53.7% of gallbladder adenocarcinomas associated with poor differentiation, lymph node metastasis, and invasion, while loss of PTEN expression was identified in 51.8% of adenocarcinomas with high grade, metastatic, and invasive tumors. Univariate Kaplan-Meier analysis showed that overexpression of EZH2 (p = 0.013) and loss of PTEN expression (p = 0.008) were significantly associated with decreased overall survival. Multivariate Cox regression analysis revealed that overexpression of EZH2 (p = 0.011) or loss of PTEN expression (p = 0.009) is a predictor of poor prognosis in gallbladder adenocarcinoma. Our study suggests that overexpression of EZH2 and loss of PTEN expression might be closely related to the carcinogenesis, progression, clinical biological behavior, and prognosis of gallbladder adenocarcinoma.     

Diagnostic accuracy of hysteroscopy in endometrial hyperplasia

Objectives: To determine the diagnostic accuracy of hysteroscopy in the diagnosis of endometrial hyperplasia in women with abnormal uterine bleeding. Methods: From 1993 through 1995, 980 women referred to our institution for abnormal uterine bleeding underwent diagnostic hysteroscopy with eye direct biopsy of the endometrium in case of macroscopic abnormalities. Hysteroscopic features were compared with pathologic findings in order to detect the reliability of the endoscopic procedure. Statistical analysis was performed with the McNemar test. Results: Positive predictive value of hysteroscopy in the diagnosis of endometrial hyperplasia accounted for 63%. In fact hysteroscopic diagnosis of endometrial hyperplasia was confirmed at pathologic examination in 81 out of 128 patients. Sensitivity and specificity of the endoscopic procedure accounted for 98% and 95%, respectively. Negative predictive value accounted for 99%, as only two cases of atypical hyperplasia were missed at hysteroscopy. Positive predictive value was higher in postmenopausal patients compared to women in the fertile age (72 vs. 58%). Conclusions: Overall, results appear encouraging, since no case of endometrial hyperplasia was missed by hysteroscopy. The high diagnostic accuracy, associated with a minimal trauma, renders hysteroscopy the ideal procedure for both diagnosis and follow-up of conservative management of endometrial hyperplasia.     

PTEN deletion and heme oxygenase-1 overexpression cooperate in prostate cancer progression and are associated with adverse clinical outcome

Overexpression of the pro-survival protein heme oxygenase-1 (HO-1) and loss of the pro-apoptotic tumour suppressor PTEN are common events in prostate cancer (PCA). We assessed the occurrence of both HO-1 expression and PTEN deletion in two cohorts of men with localized and castration-resistant prostate cancer (CRPC). The phenotypic cooperation of these markers was examined in preclinical and clinical models. Overall, there was a statistically significant difference in HO-1 epithelial expression between benign, high-grade prostatic intraepithelial neoplasia (HGPIN), localized PCA, and CRPC (p < 0.0001). The highest epithelial HO-1 expression was noted in CRPC (2.00 ± 0.89), followed by benign prostate tissue (1.49 ± 1.03) (p = 0.0003), localized PCA (1.20 ± 0.95), and HGPIN (1.07 ± 0.87) (p < 0.0001). However, the difference between HGPIN and PCA was not statistically significant (p = 0.21). PTEN deletions were observed in 35/55 (63.6%) versus 68/183 (37.1%) cases of CRPC and localized PCA, respectively. Although neither HO-1 overexpression nor PTEN deletions alone in localized PCA showed a statistically significant association with PSA relapse, the combined status of both markers correlated with disease progression (log-rank test, p = 0.01). In a preclinical model, inhibition of HO-1 by shRNA in PTEN-deficient PC3M cell line and their matched cells where PTEN is restored strongly reduced cell growth and invasion in vitro and inhibited tumour growth and lung metastasis formation in mice compared to cells where only HO-1 is inhibited or PTEN is restored. In summary, we provide clinical and experimental evidence for cooperation between epithelial HO-1 expression and PTEN deletions in relation to the PCA patient's outcome. These findings could potentially lead to the discovery of novel therapeutic modalities for advanced PCA.