Prognostic significance of paneth cell-like neuroendocrine differentiation in adenocarcinoma of the prostate

The prognostic significance of Paneth cell-like neuroendocrine differentiation in adenocarcinoma of the prostate has not yet been established. We studied 36 cases of adenocarcinoma of the prostate showing Paneth cell-like neuroendocrine differentiation, including needle biopsy specimens (n = 27), radical prostatectomies (n = 8), and transurethral resection specimens (n = 1). Paneth cell-like neuroendocrine cells (NECs) were observed as either patchy isolated cells or diffusely involving glands or nests. With Gleason pattern 3, a patchy pattern of NECs was seen in 18/19 cases with only 1/19 (5.3%) case showing diffuse NECs. All the 4 Gleason pattern 4 cases had patchy NECs. Of the 21 cases with Gleason pattern 5, 18 (85.7%) had diffuse NECs with the remaining 3 exhibiting patchy NECs. Radical prostatectomy was performed in 16/36 (44.4%). Tumor was organ confined in 10/16 cases (62.5%). Extraprostatic extension (EPE) with positive surgical margins was seen in 6/16 cases (37.5%). In 4 cases, seminal vesicles were positive for cancer. Pelvic lymph nodes were free of tumor in all cases. The actuarial prostate specific antigen progression-free risk at 5 years and 7 years was 92% and 80%, respectively. Only 2 patients progressed after radical prostatectomy and they both had Gleason score 7 cancer with extraprostatic extension and seminal vesicle invasion. Of the 16 radical prostatectomy cases, 8 (50%) had a Gleason pattern 5 component either on needle biopsy or at radical prostatectomy, with nests, cords, or single cells containing Paneth cell-like neuroendocrine differentiation. Five of these 6 cases with Gleason pattern 5 and available follow-up information had no evidence of progression with mean and median follow-ups of 46 months. Radiation therapy either as monotherapy or combined with hormonal therapy was used to treat patients in 13/36 cases. Overall only 2 patients progressed, one with clinical T2 and the other T3 disease. Of the 5 cases with Gleason pattern 5 composed in part or totally by NECs treated by radiation therapy, all are without evidence of recurrence with a mean and median follow-up of 47 and 45 months, respectively. Of the remaining 5 cases with available follow-up treated with watchful waiting, hormone therapy, or cryotherapy, 4 had Gleason pattern 5 tumor with NECs. Of these 4 cases, 3 had no progression with a mean and median follow-up of 42.5 and 60.5 months, respectively. Despite the cells' bland histologic appearance, strictly applying the Gleason grading system one would have to assign a Gleason pattern 5 to these foci with no glandular differentiation. The current study demonstrates that applying the Gleason score to these foci does not accurately reflect their clinical behavior. In cases with Paneth cell-like NECs, only the conventional adenocarcinoma component should be assigned a Gleason score. In cases in which the entire tumor is composed of Paneth cell-like cells and areas of the tumor lack glandular differentiation, the tumors should not be assigned a Gleason score and a comment should be provided as to the generally favorable prognosis of this morphologic pattern of neuroendocrine differentiation.     

Prognostic significance of the size of central fibrosis in peripheral adenocarcinoma of the lung

BACKGROUND: The prognostic significance of the characteristics of central fibrosis in peripheral adenocarcinoma of the lung has been reported. However, the prognostic significance of the size of central fibrosis has never been evaluated. METHODS: A total of 100 consecutive surgically resected peripheral adenocarcinomas of the lung measuring 3.0 cm or less in maximum dimension were reviewed histologically, and the maximum dimension of central fibrosis was measured on conventional hematoxylin and eosin stain. RESULTS: Median follow-up for patients alive was 54 months. The overall 5-year survival rate was 75%. Twenty-one patients with adenocarcinoma having central fibrosis 5 mm or smaller in maximum dimension had a 5-year survival rate of 100%, whereas the other 79 patients had a 5-year survival less than 70%. Multivariate analysis showed the size of central fibrosis to be an independent prognostic factor as significant as vascular invasion and locoregional lymph node metastasis (p = 0.010, 0.024, and 0.024, respectively). CONCLUSIONS: The size of central fibrosis is an independent prognostic factor in peripheral lung adenocarcinoma, as significant as the well-established prognostic factors vascular invasion and lymph node metastasis.     

Prostatic adenocarcinoma with marked neuroendocrine differentiation

A case is presented of prostatic cancer with marked neuroendocrine differentiation. Double-labeled immunohistochemical staining was performed with prostate-specific antigen and Chromogranin A. Both antibodies were localized to some of the cancer cells with Paneth cell-like features. Furthermore, most of the cancer cells were positively stained with luminal cell marker CAM 5.2, suggesting that neuroendocrine cells originated from the prostatic luminal cells.     

Prognostic significance of preoperative haemoglobin A1c level in patients with lung adenocarcinoma

Open in a separate window OBJECTIVESWe investigated the influence of the preoperative haemoglobin A1c (HbA1c) value on the prognosis and pathology of patients with lung adenocarcinoma who underwent surgery.METHODSWe reviewed the medical records of 400 lung adenocarcinoma patients who underwent lobectomy with mediastinal lymph node dissection between 2009 and 2013 using a prospectively maintained database. We stratified 400 patients into 4 groups according to the preoperative HbA1c value as follows: HbA1c ≤ 5.9 (n = 296), 6.0 ≤ HbA1c ≤ 6.9 (n = 70), 7.0 ≤ HbA1c ≤ 7.9 (n = 21) and HbA1c ≥ 8.0 (n = 12). We compared the recurrence-free survival and overall survival (OS) among these 4 groups. Univariate and multivariate analyses were performed to identify the risk factors for recurrence.RESULTSThe median follow-up period was 61.2 months. On comparing the recurrence-free survival and OS rates among these 4 groups, we found that these rates among patients in the HbA1c ≥ 8.0 group were significantly poorer compared with the other 3 groups (5-year recurrence-free survival: HbA1c ≤ 5.9, 70.4%; 6.0 ≤ HbA1c ≤ 6.9, 69.7%; 7.0 ≤ HbA1c ≤ 7.9, 70.7%; ≥8.0 HbA1c, 18.8%; P = 0.002; and 5-year OS: HbA1c ≤ 5.9, 88.7%; 6.0 ≤ HbA1c ≤ 6.9, 80.6%; 7.0 ≤ HbA1c ≤ 7.9, 90.2%; ≥8.0 HbA1c, 66.7%; P = 0.046). Patients in the HbA1c ≥ 8.0 group had significantly more tumours with vascular invasion (P = 0.041) and experienced distant metastasis significantly more often (P = 0.028) than those with other values. A multivariate analysis revealed that preoperative HbA1c ≥ 8.0 [hazard ratio (HR) 2.33; P = 0.026] and lymph node metastasis (HR 3.94; P < 0.001) were significant independent prognostic factors for recurrence.CONCLUSIONSOur results revealed that preoperative HbA1c ≥ 8.0 is associated to poor prognosis due to the occurrence of distant metastasis and we should carefully follow these patients after surgery.Clinical registration numberHyogo Cancer Center, G-57.     

Prognostic significance of proliferation activity and neuroendocrine differentiation to predict treatment failure after radical prostatectomy

OBJECTIVES: Neuroendocrine (NE) cells in prostate cancer may influence tumor cell proliferation in a paracrine fashion. The aims of this study were to clarify the prognostic value of tumor cell proliferation and NE tumor cell differentiation in prostate cancer after radical prostatectomy, and to compare these parameters with each other. MATERIAL AND METHODS: Specimens were pooled from a total of 528 patients treated with radical prostatectomy without neoadjuvant hormonal therapy between 1996 and 2003. NE differentiation (NED) was determined by immunohistochemistry using antibodies directed against chromogranin A (CgA), and was scored as either NE-negative (0-1+) or -positive (2-3+). Tumor cell proliferation was assessed by means of the Ki-67 labeling index (Ki-67 LI). The mean post-surgical follow-up period was 49 months (range 10-116 months). Any subsequent rise in prostate-specific antigen (PSA) level was regarded as reflecting disease progression. The prognostic values of Ki-67 and CgA were comparatively analyzed using multivariate Cox regression. RESULTS: NED was present in 6.1% of tumors. The mean Ki-67 LI was significantly higher in the CgA-positive group in comparison with CgA-negative specimens (6.6% vs 5.0%; p=0.029). The Ki-67 LI showed the highest correlations with Gleason score and pathological tumor stage (r=0.31 and r=0.3, respectively). NED was found to have the strongest association with pathological tumor stage (r=0.2). Multivariate analysis determined Gleason score > or =7 (4+3) [hazard ratio (HR) 3.04], NED (HR 1.89), lymph node metastases (HR 1.84), preoperative PSA level>20 ng/ml (HR 1.66), and Ki-67 LI > or = 5% (HR 1.62) to be significant predictors of biochemical progression. CONCLUSION: Our results identify Ki-67 LI and NED as additional prognostic markers after radical prostatectomy.     

Prognostic importance of neuroendocrine differentiation in Japanese breast cancer patients

Purpose

To evaluate the frequency and prognostic importance of neuroendocrine differentiation (NED) in Japanese breast cancer patients.

Methods

We used standard immunohistochemical techniques to examine 50 patients who underwent resection of breast cancer between 1988 and 1993 at the Department of Surgery II, Nagoya University Hospital, for NED, defined as positive reactivity for four markers: neuron-specific enolase (NSE), synaptophysin, CD57, and chromogranin A (CGA). Neuroendocrine differentiation was defined by the presence of at least one marker including CGA, CD57, and synaptophysin, or at least two markers when one was positive for NSE.

Results

Neuroendocrine differentiation was found in 13 (26%) of the 50 patients examined. There were no significant differences in the distribution of patients with positive or negative NED in terms of age, menopausal status, tumor size, lymph node metastasis, histological grade, ER, PgR, and HER2. We calculated the cumulative survival rates of patient groups according to NED status, and found no significant difference in overall or disease-free survival between patients with and those without NED.

Conclusion

Neuroendocrine differentiation was identified in a subset (26%) of Japanese breast cancer patients, but this appeared to have no relationship with established prognostic factors or patient outcome.     

Prognostic significance of lymphatic micrometastasis of esophageal adenocarcinoma

The aim of the study was to test the hypothesis that a subgroup of patients considered N0 at standard single-section pathological examination may have occult lymph-node metastases (micrometastases) associated with a poor prognosis. Fifty-nine patients with oesophageal adenocarcinoma undergoing resection were studied by standard histological examinations, serial sections and immunohistochemistry, and their long-term prognoses were compared. Eight (26%) out of 31 patients previously staged as pN0 at standard histological examination were staged as pN1 or Pn2 by serial sections and/or immunohistochemistry and had a prognosis which was significantly worse than that of true pN0 patients (5-year survival: 38% vs 76%, respectively; P < 0.05) and similar to that of pN1 patients. More than a quarter of those patients classified as pN0 at standard histological examination may have occult lymph node metastases at serial sections and/or immunohistochemistry and have a prognosis similar to that of pN1 patients.     

Prognostic significance of preoperative serum carcinoembryonic antigen level in lung adenocarcinoma but not squamous cell carcinoma.

OBJECTIVES: Clinical significance of measurement of preoperative serum carcinoembryonic antigen (CEA) level in patients with non-small cell lung cancer was investigated. METHODS: Consecutive 271 adenocarcinoma and 112 squamous cell carcinoma patients of non-small cell lung cancer referred to our institute were included in this study. There were 214 men and 169 women, ages ranged from 19 to 90 years, with an average of 64.46 years. Curative resection was performed for 220 adenocarcinoma and 93 squamous cell carcinoma patients. Serum level of CEA was measured before staging or resection of cancer. RESULTS: There is a trend toward a correlation between serum CEA level and stage of the diseases, however, serum CEA level was not always related to tumor node metastasis (TNM) status. In patients with adenocarcinoma, survival rate of patients with an elevated serum CEA level was significantly lower than that with a normal serum CEA level. Multivariate analysis showed that prognostic significance of serum CEA level was TNM staging independent in patients with adenocarcinoma. On the other hand, serum CEA level was not related to patients' survival in patients with squamous cell carcinoma. CONCLUSIONS: Elevated preoperative serum CEA level is a TNM staging independent prognostic factor for patients with adenocarcinoma but not for those with squamous cell carcinoma.     

Prognostic effect of neuroendocrine differentiation in prostate cancer: A critical review

BackgroundThe multiple pathways that are involved in neuroendocrine differentiation (NED) in prostate cancer (PCa) are poorly elucidated. Evidence suggests that several environmental triggers induce NED leading to the adaptation of PCa to its close environment to maintain cell proliferation. Nevertheless, there is conflicting evidence regarding the prognostic role of NED in PCa.MethodsIn this review, we aimed to summarize all available data about NED and to assess the prognostic role of NED in disease progression and therapy resistance, and its role in routine clinical practice. This review was based on articles found through a PubMed literature search between 1993 and 2013. The study outcome measure was the effect of NED on oncologic outcomes at each PCa stage.ResultsIn total, 59 articles reporting on the effect of NED on oncologic outcomes have been selected. In clinical practice, immunostaining for NED markers could have interesting predictive value for assessing the oncologic outcomes in patients receiving androgen-deprivation therapy. Thus, patients with high NED burden may be candidates for more aggressive treatment strategies targeting NED pathways. Conversely, strong evidence is lacking concerning its potential independent prognostic value in hormone-naïve PCa.ConclusionsCurrent published data are not sufficient to recommend the use of NE markers in routine practice, particularly at early PCa stage.     

Prognostic significance of tumour angiogenesis in schistosoma-associated adenocarcinoma of the urinary bladder

OBJECTIVE: To report on tumour angiogenesis and its relationship with morphological variables and prognosis in adenocarcinoma of the urinary bladder associated with schistosomiasis. PATIENTS AND METHODS: Fifty-five vesical adenocarcinomas were evaluated from 30 men and 25 women (mean age 47.2 years, sd 8.7, range 30-65) who were followed up after radical cystectomy and urinary diversion for a mean (sd, range) of 61 (43.5, 2.7-159.5) months. Vessels were stained immunohistochemically using an antibody to the platelet endothelial cell-adhesion molecule CD31. Microvessels were counted in active areas of angiogenesis within the tumours (at x250) and the microvessel density (MVD) quantified using the mean of three counts. Treatment failure was defined as death from cancer or the development of local recurrence or distant metastasis. Kaplan-Meier survival curves and Cox's proportional hazard model were used to assess survival. RESULTS: The overall 5- and 10-year survival rates were 57% and 51%, respectively. The presence of lymph node metastasis and high mean vascular density (> 26) were significantly associated with a poor prognosis. The 5-year survival for patients with negative lymph nodes was 66% while no patients with positive nodes survived for 5 years (P < 0.001); the survival was 72% for patients with a low MVD and 33% for those with a high MVD (P = 0.0016). From individual results plotted against vascularity in lymph node-negative patients, there was a significantly better outcome for those with a low MVD (< or = 26; P = 0.0099); this significance was maintained on multivariate analysis. However, there was no significant relationship between angiogenesis and the different clinicopathological factors apart from the grade (P = 0.03); tumour stage, grade and DNA profile had no significant effect on survival in these patients. CONCLUSIONS: These findings suggest that assessing angiogenesis using the MVD provides an independent predictor of survival in patients with adenocarcinoma of the urinary bladder.     

Prognostic value of lymphatic and blood vessel invasion in neuroendocrine tumors of the lung

Few data on the influence of vessel invasion on the progression of neuroendocrine lung tumors are available. Because of the lack of specific markers, previous studies could not reliably discriminate lymphatic and blood vessels. By immunostaining for podoplanin, specific for lymphatic endothelium, and CD34 antigen, we assessed lymphatic and blood vessel invasion in 120 tissue specimens of patients with neuroendocrine lung tumors. Lymphovascular invasion was correlated with clinicopathologic parameters, and its prognostic relevance was evaluated. Lymphatic vessels were identified exclusively at the tumor invasion front, whereas blood capillaries were also seen within tumors. Lymphatic vessel as well as lymphatic and blood vessel invasion was prevalent in patients with high-grade neuroendocrine tumors and advanced tumor stages, closely associated with lymph node metastases (P < 0.0001). In univariate analysis, these two invasion types correlated with decreased disease-free survival (both P < 0.0001), whereas blood vessel invasion alone did not. In multivariate analysis, only tumor grade and lymph node status remained statistically significant factors for prognosis (P = 0.016 and P < 0.0001). Our results suggest that evaluation of lymphatic vessel invasion is important in neuroendocrine lung tumors serving as a prognostic parameter for disease-free survival.