Pleomorphic lobular carcinoma in situ (PLCIS) on breast core needle biopsies: clinical significance and immunoprofile

Pleomorphic lobular carcinoma in situ (PLCIS) is a more recently characterized entity that mimics high-grade ductal carcinoma in situ (DCIS). PLCIS is sometimes treated similar to high-grade DCIS, but no consensus has been reached for the most appropriate treatment. The aim of this study is to evaluate the histologic and immunohistologic profile of pure PLCIS on core needle biopsies and present follow-up clinical data. We reviewed 12 cases of pure PLCIS diagnosed on core needle biopsies of the breast along with subsequent surgical resections. Histologically, all cases showed dyscohesive cells with grade 3 nuclei, prominent nucleoli, and moderate to abundant eosinophilic cytoplasm. A panel of immunohistochemical stains to study this entity included E-cadherin, P120 catenin, estrogen receptor, progesterone receptors, HER2/neu, and Ki-67 (MIB-1). Residual PLCIS was found on excisional biopsies in 83% (10/12) cases. Invasive lobular carcinoma was found in 25% (3/12) cases. The lobular nature of all cases was confirmed by negative E-cadherin and cytoplasmic-dominant staining with P120 catenin. PLCIS was positive for estrogen receptor in 92% (11/12); progesterone receptor in 50% (6/12), and Her2/neu was positive in 25% (3/12). A moderate to high proliferation activity was observed with MIB (Ki-67) staining in 92% (11/12) cases. We conclude that PLCIS has a lobular immunostaining pattern for P120 catenin and E-cadherin indicating disruption of the E-cadherin/P120 catenin complex. This entity has aggressive parameters similar to high-grade DCIS including grade 3 nuclei, high Ki-67 (MIB-1) index, and HER2/neu positivity. PLCIS has a significant association with other high-risk lesions and invasive lobular carcinoma.     

Do the histologic features and results of breast cancer biomarker studies differ between core biopsy and surgical excision specimens?

Core biopsies are commonly used in the diagnosis of breast cancer and often are the only sample for providing prognostic and predictive markers prior to neoadjuvant chemotherapy. We retrospectively studied 87 patients with breast cancer to compare the concordance rates for tumor type, grade, estrogen receptor/progesterone receptor (ER/PR), p53 status and Her2/neu by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) between core and excisional biopsy specimens. The histologic type of cancer had a 100% concordance rate between core and excisional biopsy specimens. The concordance rate of modified Bloom-Richardson score between core and excisional biopsy specimens was 77%, ER was 95%, PR was 89%, and p53 was 86%. The concordance rate for Her2/neu by IHC was 96% and that for FISH was 100% between the core and excisional biopsy specimens. Although breast cancer may have heterogeneous histological and immunohistochemical findings, our study shows that relatively high concordance rates can be obtained when comparing core and excisional biopsy specimens.     

Characteristics and clinical outcomes of pleomorphic lobular carcinoma in situ of the breast

Pleomorphic lobular carcinoma in situ (PLCIS) of the breast is a rare variant of lobular carcinoma in situ (LCIS). We reviewed 78 cases of PLCIS diagnosed at our institution from 1998 to 2012. Among all cases, 47 (60%) were associated with invasive carcinoma and/or ductal carcinoma in situ (DCIS) after final surgical excision. Of the 20 cases with PLCIS alone on core needle biopsy (CNB), 6 (30%) were upgraded to invasive carcinoma or DCIS after final surgical excision. Our findings support a recommendation for complete surgical excision of PLCIS when diagnosed on CNB.     

Adverse outcome and resistance to adjuvant antiestrogen therapy in node-positive postmenopausal breast cancer patients-The role of p53

The prognostic and predictive relevance of p53 immunoreactivity is used here as a tentative approach for defining more accurately the benefit of adjuvant hormonal therapy in postmenopausal node-positive breast cancer patients. Ninety-seven postmenopausal patients with axillary lymph node metastasis were treated with an antiestrogen for a period of 3 years after primary surgery and radiotherapy. The p53 status of the primary tumor was assessed by immunohistochemistry and 24% of the samples showed positive expression of p53. Within the average follow-up time of 59 months, disease recurrence was diagnosed in 34 patients (35%). Multivariate analysis showed high clinical stage, negative estrogen receptor status and p53 positivity to be independent prognostic factors predicting both shortened disease-free survival and worse overall survival. p53 immunoreactivity was associated with worse clinical outcome irrespective of hormone receptor status. The data suggest that adjuvant therapy with antiestrogens is insufficient in this patient population with p53-positive tumors.     

Squamous mucosal alterations in esophagectomy specimens from patients with end-stage achalasia.

Achalasia is an esophageal motor disorder in which the primary morphologic changes are found in the myenteric plexus. However, a number of secondary alterations are characteristically found in esophagectomy specimens, including the mucosa. In addition, these patients are at increased risk of developing esophageal squamous cell carcinoma. We studied the squamous mucosal alterations in 35 esophagectomy specimens from patients with end-stage achalasia and compared them with those found in the squamous mucosa near the esophagogastric junction from pediatric autopsies (相似文献   

乳腺癌中bcl-2蛋白表达的意义

为探讨抑凋亡基因ｂｃｌ－２蛋白表达在乳腺癌中的意义,应用免疫组织化学的方法,对１２５例浸润性乳腺癌患者的石蜡包埋组织切片中ｂｃｌ－２,雌激素受体,孕激素受体及ｐ＾５３基因的表达产物进行检测。结果：ｂｃｌ－２蛋白在浸润性导管癌中的表达为６３．３％,而在浸润性小叶癌中为８８．９％,二者间菜显著性间谍;在浸润性导管癌中,ｂｃｌ－２蛋白的表达与原发癌大小及肿瘤分级呈负相关,与ＥＲ,ＰＲ的表达呈正相关,与ｐ     

A comparison of prognostic tumor markers obtained on image-guided breast biopsies and final surgical specimens

BACKGROUND: This study was initiated to determine whether tumor markers obtained on image-guided breast biopsy specimens provide accurate prognostic information for women with invasive breast cancer. METHODS: Prognostic tumor markers on preoperative image-guided biopsy and final surgical specimens were compared in 44 patients with invasive breast cancer. RESULTS: Progesterone receptor (PR) discordance was 18%. In 87% of PR discordant cases, the image-guided biopsy was positive and the final specimen was negative (P = 0.03). Tumor grade was discordant in 36% of patients Discordance for estrogen receptor (ER) = 2%; MIB-1 = 18%; Her2/neu = 9%; EGFR = 10%; p53 = 9%; and bcl-2 = 0%. The discordance for these markers was random and did not reach statistical significance. CONCLUSION: Image-guided core needle biopsies provide reliable information for the majority of prognostic tumor makers. A positive progesterone receptor is significantly more likely to be determined by core biopsy rather than the final surgical specimen. Tumor grade should be based upon the final surgical specimen whenever possible.     

Correlation of her-2/neu gene amplification with other prognostic and predictive factors in female breast carcinoma

The purpose of this study was to determine if any relationship exists between Her-2/neu gene amplification and estrogen receptor (ER), progesterone receptor (PR), MIB-1, grade, size and age in female breast cancer. Five hundred and eighteen female patients with invasive breast carcinoma, 390 ductal and 128 lobular, in which assessment of Her-2/neu amplification by fluorescence in-situ hybridization (FISH) has been performed, were reviewed retrospectively. Each patient was further assessed for ER, PR, MIB-1, grade, size and age at diagnosis. Chi-square analysis was then used to correlate the above observations. Overall gene amplification was seen in 76 (15%) of the cases, 68 (17%) were ductal and 8 (6%) were lobular. Her-2/neu gene was amplified in 37 (10%) out of 379 ER positive cases and in 39 (28%) out of 139 ER negative cases. Her-2/neu was amplified in 22 (7%) out of 301 PR positive cases and in 54 (25%) out of 217 PR negative cases. Amplification occurred in 18 (8%) out of 222 negative MIB-1 cases and amplified in 58 (20%) out of 296 positive cases. Amplification was seen in 5 (10%) out of 49 grade I tumors, 17 (12%) out of 143 grade II tumors and 54 (27%) out of 198 grade III tumors. Lobular carcinomas were not graded. Amplification was present in 52 (15%) out of 346 T1 lesions, in 17 (13%) out of 130 T2 lesions, in 5 (17%) out of 30 T3 lesions and in 2 (17%) out of 12 T4 lesions. Her-2/neu was amplified in 67 (14%) out of 467 woman 41 years and older, and in 9 (18%) out of 51 women 40 years and younger. Comparison of these frequencies using chi-square test revealed statistically significant correlation between Her-2/neu amplification and ductal versus lobular carcinoma (p<0.0003), ER (p=0.0001) and PR (p<0.0001) negative tumors, over-expression of MIB-1 (p<0.0005) and high tumor grade (p=0.0009), while size of the tumor (p=0.08) and age of the patients (p=0.67) were not statistically significant. Correlation was found between Her-2/neu amplification and tumor type, high histological grade, ER and PR negative tumors, and high proliferative MIB-1 index. No correlation was found between size of the tumor and age of the patient with Her-2/neu amplification.     

Predictors of lymph node metastasis in T1 breast carcinoma,stratified by patient age

It is important to identify T1-substage breast carcinomas (BCs) which are inherently aggressive, so that these can be managed more assertively. The purpose of this study was to distinguish those T1 BCs with the potential to metastasize to axillary lymph nodes from those lacking that ability by multiparametric analysis of several clinicopathologic features. The authors studied 197 patients with invasive BC who had undergone modified radical mastectomy; 161 tumors were ductal and 26 were lobular BCs. The study group was stratified by age into two groups: ≤34 years ( n = 34) and 35–84 years ( n = 153). Pathologic lymph node status was correlated with estrogen receptor (ER) and progesterone receptor (PR) tumor positivity, MIB-1 proliferation index, and immunoreactivity for mutant p53 protein. These factors were studied immunohistologically using standard methodology and microwave-mediated epitope retrieval. Statistical analyses employed accepted techniques. Women in this study ranged from 22 to 84 years of age; 39 (21%) had positive lymph nodes. ER-positive tumors comprised 73% of the total; similarly, 65% were PR positive. The MIB-1 index was greater than 10% in 44% of lesions, and 14% demonstrated labeling for mutant p53 protein. Using crude odds ratio data, the MIB-1 index was the only indicator found to predict lymph node metastasis significantly ( p < 0.001). Moreover, even when adjustments were made for patient age, logistic regression analysis confirmed the utility of MIB-1-values of greater than 10% in this context, with a 4.4 greater likelihood of metastasis ( p < 0.001). MIB-1 indices of greater than 10% are associated with a risk of lymph node metastasis from T1 BCs, independent of patient age. Hormone receptor status and immunohistologic p53 status are not predictors of nodal involvement in this specific setting.     

Tumor marker expression is predictive of survival in patients with esophageal cancer

BACKGROUND: This study was designed to determine the prognostic value of immunohistochemical tumor marker expression in a population of patients with node-negative esophageal cancer treated with complete resection alone. METHODS: Resection specimens were collected from 61 patients with node-negative T1 (n = 31), T2 (n = 14), and T3 (n = 16) esophageal cancer. A panel of 10 tumor markers was chosen for immunohistochemical analysis, based on associations with differing oncologic mechanisms: apoptosis (p53), growth regulation (transforming growth factor-alpha, epidermal growth factor receptor, and Her2-neu), angiogenesis (factor VIII), metastatic potential (CD44), platinum resistance (p-glycoprotein and metallothionein), 5-fluorouracil resistance (thymidylate synthetase), and carcinogenic detoxification (glutathione S-transferase-pi). RESULTS: Complete resection was performed in all patients (44 adenocarcinoma, 17 squamous cell carcinoma), with no operative deaths. Multivariable analysis demonstrated a significant relationship between cancer-specific death and the following variables: low-level P-gp expression (p = 0.004), high-level expression of p53 (p = 0.04), and low-level expression of transforming growth factor-alpha (p = 0.03). In addition, the number of involved tumor markers present was strongly predictive of negative outcome (p = 0.0001). CONCLUSIONS: This study supports the prognostic value of immunohistochemical tumor markers, specifically the expression pattern of P-gp, p53, and transforming growth factor-alpha, in patients with esophageal carcinoma treated with complete resection alone.     

p53 Immunopositivity and Gene Mutation in a Group of Women at High Risk for Breast Cancer

Abstract: p53 protein overexpression and/or gene mutations have been detected in ≥50% of breast cancers and are among the most frequent changes identified in human malignancies. We examined p53 protein immunoreactivity in random periareolar breast fine needle aspirates (FNA) from 270 women at high risk for breast cancer as well as 10 in situ and invasive lesions that later developed in this cohort. We correlated p53 immunopositivity with mutational analysis performed on microdissected tumor cells. The p53 antibody PAb240 was used on acetone-fixed cytospins. Nuclear staining for p53 was detected in 29% of high-risk women. The prevalence of p53 immunoreactivity was directly correlated with cytologic abnormality and was predictive of concurrent atypical hyperplasia in a multivariate analysis (p = 0.002). Four invasive cancers, three ductal carcinoma in situ (DCIS), and three lobular carcinoma in situ (LCIS) were subsequently detected at a median follow-up time of 33 months after the initial aspiration. p53 immunopositivity was predictive of later development of DCIS and/or invasive cancer in a univariate analysis (p = 0.0026). Five of the seven women who later developed DCIS or an invasive lesion were p53 immunopositive using PAb240. One of the two remaining women had insufficient cells for p53 analysis. To examine the correlation between p53 immunoreactivity in the initial aspirate, as detected by PAb240, and the presence of p53 mutation in the 10 surgical specimens of the lesions subsequently detected, we microdissected tumor cells from paraffin sections followed by PCR-SSCP analysis for p53 exons 5–9. Immunopositivity by PAb1801 and DO-1 antibodies and a mutation in the p53 gene were detected in only one of those lesions. Microdissection studies are under way to examine FNA immunopositive cytospins for the presence of p53 mutations by PCR-SSCP analysis. At the present time we conclude that conformational changes in the p53 molecule, in the presence or absence of corresponding p53 gene mutations, may play an important role in breast carcinogenesis.     

Pleomorphic LCIS what do we know? A UK multicenter audit of pleomorphic lobular carcinoma in situ

AimsPleomorphic lobular carcinoma in situ (PLCIS) is a relatively newly described pathological lesion that is distinguished from classical LCIS by its large pleomorphic nuclei. The lesion is uncommon and its appropriate management has been debated. The aim of this study is to review data from a large series of PLCIS to examine its natural history in order to guide management plans.Materials and methodsComprehensive pathology data were collected from two cohorts; one from a UK multicentre audit and the other a series of PLCIS cases identified from within the GLACIER study cohort. 179 cases were identified of whom 176 had enough data for analysis.ResultsOut of these 176 cases, 130 had invasive disease associated with PLCIS, the majority being of lobular type (classical and/or pleomorphic). A high incidence of histological grade 2 and 3 invasive cancers was noted with a predominance of ER positive and HER-2 negative malignancy. When PLCIS was the most significant finding on diagnostic biopsy the upgrade to invasive disease on excision was 31.8%, which is higher than pooled data for classical LCIS and DCIS.ConclusionThe older age at presentation, high grade of upgrade to invasive cancer, common association with higher grade tumours suggest that PLCIS is an aggressive form of insitu disease. These findings support the view that PLCIS is a more aggressive form of lobular in situ neoplasia and supports the tendency to treat akin to DCIS.     

p53, bcl-2 and Retinoblastoma Proteins as Long-Term Prognostic Markers in Localized Carcinoma of the Prostate

Purpose

The accumulation of p53 and bcl-2 gene products as well as the loss of the retinoblastoma (Rb) gene product have been associated with prostate cancer progression. We assessed whether the levels of immunoreactivity for p53, Rb and bcl-2 are better long-term predictors of disease specific survival than conventional pathological parameters of the primary tumor, such as Gleason score, capsular penetration, seminal vesicle invasion, and percent tumor in the specimen, in patients with clinically localized prostate cancer treated with radical prostatectomy.

Materials and Methods

A total of 71 patients with clinical stages A1 to B2 adenocarcinoma of the prostate underwent radical prostatectomy after a negative metastatic evaluation. No neoadjuvant or adjuvant treatments were given and causes of death were recorded. Prostatectomy specimens were analyzed to determine the conventional pathological parameters, and p53, Rb and bcl-2 immunohistochemical staining. Univariate and multivariate analyses were done to determine the independent contributions of p53, Rb and bcl-2 in predicting survival.

Results

On multivariate analysis the independent factors predicting disease specific survival were p53 staining score (p <0.001) and Rb staining score (p <0.001). In patients with p53 immunoreactive tumors the 15-year disease specific survival was 38% compared to 87% for those with less immunoreactivity. Analysis of Rb immunoreactivity for 15-year disease specific survival yielded 92 and 66% high and low staining levels, respectively. Best subset analysis revealed that the combination of p53 score and Rb score yielded the best predictive value for disease specific survival.

Conclusions

p53 and Rb immunohistochemical staining scores were independent predictors of disease specific survival and were superior to conventional pathological prognostic factors of the primary tumor. These findings lay the groundwork for the prospective study of these markers in patients treated with radical prostatectomy.     

LOCALLY RECURRENT PROSTATE TUMORS FOLLOWING EITHER RADIATION THERAPY OR RADICAL PROSTATECTOMY HAVE CHANGES IN KI-67 LABELING INDEX, P53 AND BCL-2 IMMUNOREACTIVITY

Purpose

We compare the biological phenotype of recurrent prostatic tumors after definitive local therapy (radiation or radical prostatectomy) with that of the same tumors before treatment.

Materials and Methods

Cellular proliferation (Ki-67 labeling index), p53 nuclear reactivity and bcl-2 immunoreactivity were determined in pretreatment and posttreatment tumor specimens from 13 patients with local tumor recurrence following radiation, and in 18 patients with local tumor recurrence following radical prostatectomy.

Results

Mean Ki-67 labeling index increased approximately 2-fold in locally recurrent tumors after radiation (10.5 versus 5.6%, p = 0.0008) or surgery (6.0 versus 3.2%, p = 0.0025) when compared with pretreatment tumors. We noted p53 nuclear reactivity in a significantly higher proportion of recurrences than in pretreatment tumors following radiation (54 versus 8%, p = 0.032) and surgery (39 versus 5%, p = 0.022). Although bcl-2 immunoreactivity was also seen in a higher proportion of recurrent tumors, this difference did not reach statistical significance for either radiation or surgery.

Conclusions

Recurrent tumors following either radiation or surgery differ significantly from the corresponding pretreatment tumors with respect to cellular proliferation and p53 nuclear reactivity.     

Clinicopathologic and immunohistochemical characteristics of male breast cancer: a single center experience

Male breast cancer (MaleBC) is a rare tumor that has been insufficiently described in the Middle East. The purpose of this study is to report the first MaleBC series in Lebanon, describing its clinicopathologic and immunohistochemical phenotype, and how it compares with MaleBC in the West and with female breast cancer in Lebanon and the Middle East. Forty-seven cases of MaleBC were reviewed. Results showed younger ages at presentation (62 years versus 67 years), higher incidence of lobular carcinoma (6% versus 1%), and more frequent p53 positivity and axillary node metastases in our series than in those reported about MaleBC. Other results such as higher estrogen receptor (ER) positivity and lower HER-2/neu over-expression were comparable to the literature. These findings suggest that MaleBC in our region may represent a biologically different tumor with potentially distinct prognostic and therapeutic implications.     

Breast Carcinoma versus Lung Adenocarcinoma: The Immunohistochemical Discrimination of Breast Carcinoma Metastatic in Lung

Abstract: Breast and lung adenocarcinomas are the two neoplasms with the highest incidence in women, and as a result, these tumors are some of the most frequently seen tumors in surgical pathology and fine-needle aspiration biopsies. The number of patients having both tumors is on the rise. For therapeutic purposes, it is important to be able to distinguish the two in tissues and in fine-needle aspirates (FNA).
Formalin-fixed, paraffin-embedded archival tissue from ductal and lobular breast carcinomas metastatic to lung (29 cases), ductal breast carcinomas (18 cases), and pulmonary adenocarcinomas (15 cases) were examined by light microscopy and by a battery of antibodies, including monoclonal CEA, monoclonal CEA-D14, GCDFP-15, alphalactalbumin, vimentin, S-100 protein, and estrogen-receptor protein. The avidin-biotin immunoperoxidase method was used. Sensitivity and specificity were analyzed and compared with each other using Youden's J statistic. In the lung, CEA-D14 was the single best antibody for identifying lung tumors while GCDFP-15 and estrogen receptor (ER) were the antibodies that best identify metastatic breast carcinoma in the lung. Because of the focal nature of GCDFP-15 staining in many metastatic tumors, this antibody may be less useful for discrimination of breast carcinomas in small biopsies and FNA specimens.     

p53 Protein and Gene Alterations in Pathological Stage C Prostate Carcinoma

Purpose

We determined the extent of p53 immunoreactivity in pathological stage C prostate cancer as well as its correlation to tumor grade, substage, recurrence and proliferation rate. To define better the temporal relationship of p53 nuclear reactivity in prostate cancer p53 immunoreactivity was evaluated in all associated prostatic intraepithelial neoplasia lesions.

Materials and Methods

Using immunohistochemistry p53 status and proliferation rate were determined in 96 tumors from patients with pathological stage C prostate cancer. Single strand conformational polymorphism in exons 5 to 8 was used in a subset of specimens to assess the association of p53 nuclear accumulation with mutations in the p53 gene.

Results

p53 Nuclear reactivity was demonstrated in 10 tumors (10.4%), including 6 with high and 4 with low level nuclear reactivity. Of the tumors 86 (89.6%) had no evidence of p53 immunoreactivity. Each of the 6 tumors with high level p53 reactivity had associated areas of prostatic intraepithelial neoplasia that also showed p53 nuclear reactivity. Furthermore, pathological stage C substage (C1, 2 or 3) was significantly associated with p53 nuclear reactivity (p = 0.04). Proliferation rates were correlated with p53 nuclear reactivity (p = 0.09), while there was no association with tumor grade or recurrence. p53 Gene alterations were noted in 2 of the 3 p53 positive tumors versus no alterations in the p53 gene of 3 p53 negative tumors.

Conclusions

p53 Nuclear accumulation is uncommon in pathological stage C prostate cancer and its presence in premalignant prostatic intraepithelial neoplasia lesions suggests that it may be an early event in a subset of prostate cancers.     

GATA3、MGB和GCDFP-15在乳腺癌中的病理诊断价值

目的探讨GATA结合蛋白3(GATA3)、乳腺珠蛋白(MGB)和巨囊性病液体蛋白-15(GCDFP-15)在乳腺癌中的病理诊断价值。方法采用免疫组化方法检测GATA3、MGB、GCDFP-15、雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(HER2)、Ki67在乳腺癌中的表达,并根据组织来源及免疫表型将乳腺癌分为原发性/转移性乳腺癌、激素受体阳性/阴性乳腺癌及不同分子分型的乳腺癌,统计GATA3、MGB、GCDFP-15阳性率。结果GATA3在原发性/转移性乳腺癌中的阳性率(92.5%;94.25%)均显著高于MGB(42.11%;29.17%)和GCDFP-15(55.77%;31.34%)(P<0.01),对于评估原发灶不明来源的肿瘤,尤其是恶性积液的标本,GATA3具有更好的敏感性。此外,MGB和GCDFP-15在激素受体阴性和三阴型乳腺癌中的阳性率偏低,进一步加大了这两种转移性乳腺癌的诊断难度。而GATA3在激素受体阴性(90.38%)或三阴型乳腺癌中的阳性率(85.29%)显著高于MGB(20.00%;5.00%)和GCDFP-15(35.09%;33.33%)(P<0.01),提示其在激素受体阴性和三阴型转移性乳腺癌中具有潜在诊断价值,是一个优于MGB和GCDFP-15的特异性标记物。结论对于评估原发灶不明来源的肿瘤,尤其是恶性积液的标本,或免疫表型为激素受体阴性和三阴性的乳腺癌,GATA3具有比MGB和GCDFP-15更高的诊断价值。     

Impact of triple negative phenotype on breast cancer prognosis

Triple negative (TN) [estrogen receptor (ER), progesterone receptor (PgR)] (ER-/PgR-/Her2/neu-) breast cancer (BC) is an aggressive disease without tumor-specific treatment options. Our objective is to evaluate the relative contribution of combined Her2/neu (Her2) and hormone receptor (HR) status to BC progression. A prospective primary BC cohort of 1550 patients at our institution, stage I-IV, from 1998 to 2003 were categorized by HR and Her2 status into ER+/PgR+/Her2- (HR+/Her2-) (n = 1134), ER+/PgR+/Her2+ [triple positive (TP)] (n = 138), ER-/PgR-/Her2- (TN) (n = 183), and ER-/PgR-/Her2+ (HR-/Her2+) (n = 95). Clinical variables were chart abstracted and vital and disease status updated annually. Log-rank tests and Cox regression analyses were used to assess associations with survival. Patient age ranged from 21 to 88 years and average length of follow-up was 4.24 years. Overall survival at 5 years was 94% (HR+/Her2-), 91% (TP), and 81% (TN and HR-/Her2+) (log rank test = 22.22, p < 0.001). Disease-specific survival at 5 years was 98% (HR+/Her2-), 93% (TP), 88% (TN), and 86% (HR-/Her2+) (log rank test = 25.85, p < 0.001) and 5-year relapse-free survival was 95% (HR+/Her2-), 89% (TP), 84% (TN), and 76% (HR-/Her2+) (log rank test = 20.29, p < 0.001). In a model adjusted for age, race, TNM stage, and treatment using HR+/Her2- patients as the reference group, recurrence risk was 1.98 for TP (95% CI = 1.02 to 3.84), 2.32 for TN (95% CI = 1.32 to 4.08), and 4.25 for HR-/Her2+ patients (95% CI = 2.33, 7.75). A hierarchy of BC phenotypes defined by HR and Her2 status exists with progressively worse disease outcomes by category.     

The role of p53, bcl-2 and E-cadherin expression in predicting biochemical relapse for organ confined prostate cancer in Taiwan

PURPOSE: We evaluated the prognostic significance of p53, bcl-2 and E-cadherin immunoreactivity for organ confined prostate cancer after radical prostatectomy. MATERIALS AND METHODS: The medical records on 70 pT2 prostatic adenocarcinomas were analyzed retrospectively. Radical prostatectomy specimens were stained using antip53 (DO7), antibcl-2 (124) (Dako, Glostrup, Denmark) and antiE-cadherin (HECD-1) (R & D Systems, Abingdon, United Kingdom) antibodies. Biochemical relapse was defined as 2 consecutive elevations in serum prostatic specific antigen (PSA) higher than 0.2 ng/ml. The prognostic significance of Gleason grade, PSA, and p53, bcl-2 and E-cadherin expression was assessed. RESULTS: While p53 immunoreactivity was identified in 16 patients (22.9%), only 3 tumors (4.3%) expressed bcl-2. Aberrant E-cadherin expression was noted in 39 tumors (55.7%). At a median followup of 36.5 months 21 patients (30%) experienced biochemical relapse. There was a significantly higher biochemical failure rate in patients with abnormal bcl-2 and E-cadherin expression (log rank test p = 0.024 and 0.003, respectively). On multivariate analysis bcl-2 and E-cadherin contributed independently to the prediction of PSA relapse (p = 0.017 and 0.005, respectively). CONCLUSIONS: We noted that bcl-2 and aberrant E-cadherin expression are independent factors predicting biochemical relapse in stage pT2 prostatic cancers.