Tumor Deposits In Lymph Nodes Research Articles

Stereotactic Body Radiation Therapy Salvage for Lymph Node Recurrent Prostate Cancer in the Era of PSMA PET Imaging.

Our understanding of patterns of prostate cancer recurrence after primary treatment of localized disease has significantly evolved since the development of positron emission tomography (PET) agents targeting prostate cancer. Previously, most biochemical recurrences were not associated with imaging correlates when restaging with computed tomography (CT), magnetic resonance imaging (MRI), or bone scintigraphy and, hence, were typically assumed to represent occult metastases. A rising prostate specific antigen (PSA) after previous local therapy prompting a PET scan showing uptake limited to regional lymph nodes is an increasingly common clinical scenario as advanced prostate cancer imaging becomes more widely utilized. The optimal management strategy for patients who have lymph node recurrent prostate cancer is both unclear and evolving, particularly in terms of local and regionally directed therapies. Stereotactic body radiation therapy (SBRT) utilizes ablative radiation doses with steep gradients to achieve local tumor control while sparing nearby normal tissues. SBRT is an attractive therapeutic modality due to its efficacy, favorable toxicity profile, and flexibility to administer elective doses to areas of potential occult involvement. The purpose of this review is to briefly describe how SBRT is being implemented in the era of PSMA PET for the management of solely lymph node recurrent prostate cancer. SBRT has been shown to effectively control individual lymph node tumor deposits within the pelvis and retroperitoneum for prostate cancer and is well-tolerated with a favorable toxicity profile. However, a major limitation thus far has been the lack of prospective trials supporting the use of SBRT for oligometastatic nodal recurrent prostate cancer. As further trials are conducted, its exact role in the treatment paradigm of recurrent prostate cancer will be better established. Although PET-guided SBRT appears feasible and potentially beneficial, there is still considerable uncertainty about the use of elective nodal radiotherapy (ENRT) in patients with nodal recurrent oligometastatic prostate cancer. PSMA PET has undoubtedly advanced imaging of recurrent prostate cancer, revealing anatomic correlates for disease recurrence that previously went undetected. At the same time, SBRT continues to be explored in prostate cancer with feasibility, a favorable risk profile, and satisfactory oncologic outcomes. However, much of the existing literature comes from the pre-PSMA PET era and integration of this novel imaging approach has led to greater focus on new and ongoing clinical trials to rigorously evaluate this approach and compare to other established treatment modalities utilized for oligometastatic, nodal recurrence of prostate cancer.

Prognostic Importance of Nodal Microenvironment beyond Extracapsular Extension in Breast Cancer Outcomes

<h3>Purpose/Objective(s)</h3> Lymph node (LN) involvement and extracapsular extension (ECE) play important roles in breast cancer risk stratification, management, and outcome. Involvement of other axillary tissues (AXT) excised during surgery is often omitted in pathology reports and its prognostic significance is yet to be elucidated. <h3>Materials/Methods</h3> Medical records of 1,919 breast cancer patients with pathologic lymph nodes treated at our institution from 2000-2019 was retrospectively reviewed. Extensive details of LN involvement are reported by pathologists at our institution and were divided into 4 groups: LN+ only, LN+ECE, LN+AXT without ECE, and LN+ECE+AXT. AXT was defined as the involvement of lymphatic vessels, blood vessels, soft tissue metastasis, matted unspecified masses and combination of any of those forms. The primary endpoint was the impact of AXT on locoregional failure (LRF) defined as recurrence in either breast/chest wall/axilla/supraclavicular fossa, on axillary failure (AF) defined as recurrence in the axilla only and on distant failure (DF) defined as metastasis. Subgroup analysis explored the differences between types of AXT and Cox Hazard models were used. <h3>Results</h3> Among 1,919 patients analyzed, 995 had LN+ only involvement, 534 had LN+ECE, 81 had LN+AXT without ECE, and 309 had LN+ECE+AXT. The overall median follow-up was 6.5 years. The 10 years cumulative incidence of LRF was 5.9%, 6.4%, 11.8% and 10.9% in LN only, LN+ECE, LN+AXT without ECE and LN+ECE+AXT groups, respectively. The 10 years cumulative incidence of AF was 0.92%, 0.83%, 4.1% and 4.4% in LN+ only, LN+ECE, LN+AXT without ECE and LN+ECE+AXT groups, respectively. The 10 years cumulative incidence of DF was 15.7%, 23%, 23.5% and 42.1% in LN+ only, LN+ECE, LN+AXT without ECE and LN+ECE+AXT groups, respectively. On multivariable analysis controlling for number of malignant LN, ECE, tumor biology, grade and size, type of axillary surgery and radiation dose delivered to the draining lymphatics, the presence of other AXT was significantly associated with LRF (HR:2.3, P<0.01), AF (HR:4.7, P<0.01) and DF (HR: 1.4, P=0.02). ECE and number of malignant LN were not associated with LRF and AF, but rather associated with DF (HR:1.4, P=0.009 and HR:1.03, P=0.002, respectively). Delivery of 50 Gy or more to draining lymphatics was associated with better axillary control (HR:0.3, P=0.01) compared to 45 Gy. No significant difference between 45 Gy and 50 Gy to the lymphatics was observed for LRF and DF. Subgroup analysis did not show a difference between the described forms of AXT on LRF and DF. <h3>Conclusion</h3> Pathologic evaluation of the axilla's microenvironment beyond tumor deposits in lymph nodes and ECE is important to ensure adequate local control in the axilla. Given the higher risk of recurrence posed by tumor infiltration into surrounding axillary tissues, delivery of at least 50Gy to lymphatics should be considered. Our findings demonstrate the need for pathology reports to include assessment of the axilla's microenvironment.

MP57-01 THE DIAGNOSTIC ACCURACY OF 68GA-PSMA-PET/CT FOR DETECTION OF LYMPH NODE METASTASES IN THE SETTING OF SALVAGE LYMPH NODE DISSECTION

INTRODUCTION AND OBJECTIVES: Accurate imaging of lymph node metastases (LNM) is a prerequisite for metastases directed therapies such as salvage lymph node dissection (salvage-LND) in nodal recurrent prostate cancer (PCa). Our aim was to evaluate the diagnostic accuracy of 68PSMA-PET/CT (DKFZ-11) for nodal relapse of PCa according to different topographical locations and the size of tumor deposits in lymph nodes (LN). METHODS: 25 patients with the suspicion of nodal PCa-relapse after primary therapy underwent pelvic and/or retroperitoneal salvage-LND after a whole body PET/CT with 68Ga-PSMA showing PET-positive lesions. Time from PET/CT to salvage-LND was median 2.3 months. Diagnostic accuracy of PET/CT for dissected main-regions (pelvic left/right, retroperitoneal) and subregions (common, external, internal iliac, obturatoria, presacral, aortic-bifurcation, aortal, caval, interaortocaval) was determined by comparing histopathologic results with PET/CT-findings. Size ofmetastatic infiltration inLNwasmeasuredbasedonhistopathology. RESULTS: Mean PSA at salvage-LND was 3.03 ng/ml (SD 3.2 / median 1.74 ng/ml). Overall, 833 LN were resected in 25 patients, containing 98 LNM, corresponding to a mean of 33.3 LN and 3.9 LNM per patient. In 5 patients (8 subregions) tissue containing solid non-nodal local relapse was additionally resected. LN were removed in portions out of 10 subregions per patient leading to 251 subregions available for evaluation. Median 3 LN were removed per subregion. For 2/25 patients and in 7/251 subregions, the suspected tumor involvement was verified by follow-up PET/CT showing progress of the lesions and PSA increase. 35/60 (58.3%) of the main regions and 63/251 (25%) of the subregions were PET-positive. Sensitivity, specifity, positive predictive value (PPV), negative predictive value (NPV) and accuracy based on a main-region analysis was 92.1% (35/38), 100% (22/22), 100% (35/35), 88.0% (22/25) and 95.0% (57/60). Based on a subregion-analyses sensitivity, specifity, PPV, NPV and accuracy was 80.7 % (63/78), 100% (173/173), 100% (63/63), 92.0% (173/188) and 94.0% (236/251). Median diameter (6 mm) of tumor deposits in LNM removed from true-positive subregions was significantly different to LNM resected from false-negative subregions (2 mm) (p<0.0001). CONCLUSIONS: 68PSMA-PET/CT shows high diagnostic accuracy for detection of LNMand served therefore as an essential guidance for salvage-LND. LNM removed from false-negative subregions were significantly smaller compared to LNM removed from true-positive subregions.

Invasive Micropapillary Carcinoma of the Breast: Immunophenotypic Analysis and Role of Cell Adhesion Molecules (CD44 and E-Cadherin) in Nodal Metastasis.

Invasive micropapillary carcinoma is a morphologically distinct subtype of breast carcinoma with high frequency of lymph node metastasis. In this study, we analyzed clinicopathologic features, immunophenotype, and expression of adhesion molecules [CD44 and E-cadherin (E-Cad)] in pure invasive micropapillary carcinoma of the breast. All cases had diffuse micropapillary pattern and were grade II tumors. Lymphovascular emboli were present in 80% and lymph node tumor deposits were seen in 69.2% cases. The cases were classified as; luminal A (11 cases), luminal B (8 cases), Her-2-neu overexpressing (4 cases), and triple negative (2 cases). All cases were positive for luminal cytokeratin (CK)CK8/18, and 2 cases showed <10% positivity for CK5/6. Eighteen cases showed loss of CD44 expression and 7 cases showed only weak positivity. Seven cases with lymph node metastasis showed reexpression of CD44 at metastatic site. Strong to moderate expression of E-Cad was observed in all cases and the corresponding nodal metastasis. To conclude, the loss of the CD44 expression plays role in lymphovascular permeation and metastasis and it can be hypothesized that its reexpression at metastatic site may play a role in homing of tumor cells. However, intact E-Cad expression could be because of the fact that tumour cells travel as clusters and retain their expression of E-Cad.

Surgery for colon cancer – complete mesocolic excision

This review presents the concept of complete mesocolic excision (CME) for colon carcinomas. It focuses on an anatomical preparation in embryological preformed planes. Different tumour locations require individual operative strategies. In contrast to other malignancies, lymphatic metastasis in colon cancer is initially based on fixed rules. The extent of lymph node dissection and mesocolic resection for each tumour depends on the location of potential tumour deposits in lymph nodes along supplying arteries and aberrant lymph node stations.

Lymph node metastasis: A bearing on prognosis in squamous cell carcinoma.

Nodal status is a significant predictor for survival of patients with oral squamous cell carcinoma (SCC), sentinel lymph node (SLN) biopsy, step sectioning of SLNs, and immunohistochemistry have changed the detection of tumor deposits in lymph nodes (LNs). The extent of LN metastasis is a major determinant for the staging and the prognosis of most human malignancies and often guides therapeutic decisions. Metastasis to regional lymph node (RLN) is a complex process. It is often associated with several clinical and pathological characteristics. The involvement of RLN is often, a harbinger for increased risk of metastasis. New knowledge in this area can enable the clinicians and pathologists to study and treat tumors in a more directed fashion. A molecular approach to factors that predicts the likelihood of RLN metastasis could eliminate the reoccurrence of the tumor in the form of "micrometastasis" and "skip" metastasis. The aim of this review is to discuss different modes of spread of metastasis in SCC.

Feasibility study of sentinel lymph node biopsy in esophageal cancer with conservative lymphadenectomy

Lymphoscintigraphy and sentinel node mapping is established in breast cancer and melanoma but not in esophageal cancer, even though many centers have shown that occult tumor deposits in lymph nodes influence prognosis. We report our initial experience with lymphoscintigraphy and sentinel lymph node biopsy in patients undergoing resection for esophageal cancer. Sixteen of 17 consecutive patients underwent resection for invasive esophageal cancer along with sentinel lymph node retrieval (resection rate, 94%). Peritumoral injection of (99m)Tc antimony colloid was performed by upper endoscopy prior to the operation. A two-surgeon synchronous approach via right thoracotomy and laparotomy was performed with conservative lymphadenectomy. Sentinel lymph nodes were identified using a gamma probe both in vivo and ex vivo. Sentinel lymph nodes were sent off separately for serial sections and immunohistochemistry. Median patient age was 60.4 years (range, 45-75 years). Fifteen were male, and thirteen had adenocarcinoma. At least one sentinel lymph node (median, 2) was identified in 14 of 16 patients (success rate, 88%). Sentinel nodes were present in more than one nodal station in five patients (31%). In all 14 patients, the sentinel lymph node accurately predicted findings in non-sentinel nodes (accuracy, 100%). Three patients with positive sentinel lymph nodes had metastases identified in non-sentinel nodes (sensitivity, 100%). Sentinel lymph node biopsy is feasible in esophageal resection with conservative lymphadenectomy, and initial results suggest it is accurate in predicting overall nodal status. Further study is needed to assess impact on patient management and prognosis.

Expression of E-Cadherin in breast carcinomas and its association with other biological markers — a prospective study

E-cadherin (E-CD) is an important cell adhesion molecule in normal epithelial cells and has been shown to be an invasion tumor suppressor gene. Various clinicopathological parameters like age, family history, tumor stage, histological grade, lymph node status and other biological markers were also analyzed. Present study reveals E-CD expression in 65 cases of breast cancer including 41 (63%) cases of pure infiltrating ductal carcinoma (IDC), 11 (16.9%) of pure infiltrating lobular carcinoma (ILC); another 10 (15.3%) of mixed ductal/lobular type, and remaining 3 (4.6%) miscellaneous types. Negative E-CD expression was noticed more in advancing age groups (P = 0.01). About 59.2% cases showing negative E-CD expression had family history of breast and/or other cancers. E-CD expression was found significantly higher in cases of pure IDC (55.5%) than in pure ILC cases (18.1%) (P = 0.04). Eleven (68.7%) of the total 16 high-grade IDC cases, revealed negative expression. Both cases of comedo carcinoma revealed negative expression. Three (30%) out of 10 mixed cases revealed negative expression in both ductal and lobular areas, while in remaining 7 cases, positvity was seen in ductal areas only. Invasive cribriform and medullary carcinoma revealed a stronger expression, while negative staining was observed in sweat gland carcinoma. E-CD re-expression was noticed in lymph node tumor deposits. A direct association of E-CD expression with ER expression and an inverse association with that of p53 were also observed (P = 0.001), (P = 0.04). E-CD expression is useful, but limited, in differentiating IDCs from ILCS. Its negative expression correlates with certain poor prognostic parameters reflecting its use as a marker for invasive cancers. It re-expresses at metastatic sites.

Detection of occult tumor cells (OTC) and micrometastases (MM) in axillary lymph node by microscopic ultrastaging

Purpose: Early breast cancer presents with a remarkable heterogeneity of outcomes. Undetected, microscopic lymph node tumor deposits may account for a significant fraction of this prognostic diversity. About 10% of nodal negative patients may represent OTC/MM in axillary nodes (Querlozi et al. 2006). So, axillary nodes were investigated immunohistochemically. OTC were defined as tumor cell deposits within the nodes measuring <0.2mm and MM measuring >0.2mm, but <0.2cm (Hermanek et al. 1999).

Axillary Lymph Node Nanometastases Are Prognostic Factors for Disease-Free Survival and Metastatic Relapse in Breast Cancer Patients

Early breast cancer presents with a remarkable heterogeneity of outcomes. Undetected, microscopic lymph node tumor deposits may account for a significant fraction of this prognostic diversity. Thus, we systematically evaluated the presence of lymph node tumor cell deposits<or=0.2 mm in diameter [pN0(i+), nanometastases] and analyzed their prognostic effect. Single-institution, consecutive patients with 8 years of median follow-up (n=702) were studied. To maximize chances of detecting micrometastases and nanometastases, whole-axilla dissections were analyzed. pN0 cases (n=377) were systematically reevaluated by lymph node (n=6676) step-sectioning and anticytokeratin immunohistochemical analysis. The risk of first adverse events and of distant relapse of bona fide pN0 patients was compared with that of pN0(i+), pN1mi, and pN1 cases. Minimal lymph node deposits were revealed in 13% of pN0 patients. The hazard ratio for all adverse events of pN0(i+) versus pN0(i-) was 2.51 (P=0.00019). Hazards of pN1mi and pN0(i+) cases were not significantly different. A multivariate Cox model showed a hazard ratio of 2.16 for grouped pN0(i+)/pN1mi versus pN0(i-) (P=0.0005). Crude cumulative incidence curves for metastatic relapse were also significantly different (Gray's test chi2=5.54, P=0.019). Nanometastases are a strong risk factor for disease-free survival and for metastatic relapse. These findings support the inclusion of procedures for nanometastasis detection in tumor-node-metastasis staging.

Axillary lymph node nanometastases are prognostic factors for metastatic relapse in breast cancer patients

610 Background: Early breast cancer presents with a remarkable and largely unaccounted for heterogeneity of outcomes. Undetected, microscopic lymph node tumor deposits may account for a significant fraction of this prognostic diversity. Thus, we systematically evaluated the presence of lymph node tumor cell deposits &lt;0.2 mm in diameter [pN0(i+), nanometastases], and analysed their prognostic impact. Methods: Seven hundred and two single institution, consecutive patients with 8 years of median follow-up were studied. To maximize the chances of detecting micro and nanometastases, whole-axilla dissections were analysed. pN0 cases were systematically reevaluated by step sectioning and anti-cytokeratin immunohistochemical analysis of 6676 corresponding dissected lymph nodes. The risk of first adverse events and of distant relapse of bona fide pN0 patients was compared with that of pN0(i+), pN1mi and pN1 cases. Crude cumulative incidence (CCI) curves were used to estimate the cumulative probability of occurrence of adverse events. CCI curves were compared by the Gray’s test. A proportional sub distribution hazard (SDH) regression model was utilized to assess the difference among CCI curves of pN0(i+) versus pN0(i-), and of pN1mi versus pN0(i+). Competing risks were accounted for and regression models were adjusted for established breast cancer prognostic factors, i.e. grading, pathological T stage and age. Proportional SDH assumptions were checked using Schoenfeld-type residuals. Results: A pN0(i+) status was shown to be a strong risk factor for event-free survival (P&lt;0.0005) and for metastatic relapse in both univariate and multivariate analyses accounting for competing risks and adjusted for grading, pathological T stage and age. Conclusions: Our findings demonstrate that nanometastases are an important risk factor in breast cancer. These results support the inclusion of procedures for nanometastasis detection in TNM pathological staging. No significant financial relationships to disclose.

Presence and maturity of dendritic cells in melanoma lymph node metastases

Immune avoidance mechanisms play a key role in the successful dissemination of melanoma. One mechanism whereby this could be achieved is by interfering with dendritic cell (DC) presentation of tumour-associated antigens to naïve T cells. In particular, immature DCs characterized by the absence of accessory molecules are known to be immunosuppressive and to be involved in the induction of tolerance. The present study has investigated the presence and activation status of DCs within melanoma metastases in the regional lymph nodes. Using image analysis techniques, the expression of Factor XIIIa (FXIIIa), CD40, CD83 and HLA-DR and the morphological features of DCs were examined in paraffin sections from 26 lymph nodes containing melanoma metastases. DCs expressing FXIIIa were found in 70% of the lymph nodes. The number of DCs identified was generally small but there were more concentrated areas of DCs designated as hotspots. In these areas of high FXIIIa staining, the percentage area occupied by DCs varied between 0.1% and 10%. The majority of FXIIIa-positive cells did not express the DC maturation markers CD83 or CD40 and morphologically were rounded with few dendrites, indicating that they were immature. The cells did, however, express high levels of HLA-DR, suggesting that they have the ability to present antigen but lack the accessory molecules required to initiate an immune response. Immature DCs, characterized by phenotypic and morphological features, are therefore present within the tumour deposits in lymph nodes infiltrated by melanoma and may specifically modulate the anti-melanoma immune response.

FDG-PET sensitivity for melanoma lymph node metastases is dependent on tumor volume.

The purpose of this study is to determine the tumor volume threshold for successful positron emission tomography (PET) imaging of melanoma nodal metastases. Review of a clinical series of patients who had FDG-PET imaging of regional lymph node basins followed by lymphadenectomy. Lymph node tumor volumes were calculated from direct measurements of metastatic nodule(s) in formalin fixed specimens. PET scan interpretations were correlated with histology to determine sensitivity. Sensitivity was correlated with the aggregate lymph node tumor volume in the nodal basin and with AJCC stage group. Forty-five patients with 49 pathologically positive regional nodal basins comprised the study group. Median total basin tumor volume was 28.3 mm(3)(range 0.004-22,879 mm(3)). FDG-PET sensitivity for detection of all tumor volumes was 0.49. The observed 90% sensitivity threshold for detection of nodal metastases was > or = 78 mm(3). PET sensitivity was 0.14 for detection of tumor volumes < 78 mm(3). PET sensitivity differed by prescan AJCC stage: I-0.0; II-0.24; III-0.81; IV-1.0 (P < 0.001). FDG-PET reliably detects lymph node tumor deposits greater than approximately 80 mm(3) volume, but sensitivity falls rapidly below this. This amount of tumor is most likely to occur in patients with AJCC stage III or IV disease.

New Lessons From the Sentinel Node

Sentinel node biopsy to determine the presence of metastatic disease in regional lymph nodes has been described in a variety of solid tumors. Sentinel node biopsy has proven that drainage of cancer cells to the regional lymph nodes is an orderly process with metastasis predominantly to one or two nodes first before involvement of subsequent nodes. The use of this technique has resulted in the increased identification of regional metastasis suggesting that patients previously identified as node negative may have unidentified regional metastasis. The clinical significance of these microscopic tumor deposits in lymph nodes remains controversial.

Epidermal growth factor receptor immunoreactivity in human laryngeal squamous cell carcinoma

Epidermal growth factor receptor (EGFR) is a transmembrane protein receptor with tyrosine kinase activity. The protein has cysteine-rich sequence repeats in its extracellular ligand-binding domains. Elevated levels of EGFR are associated with malignant transformation of squamous cells and are observed in squamous cell carcinomas from the lung, head, neck, skin, cervix and esophagus. We examined the expression of EGFR in laryngeal squamous cell carcinoma (SCC) (N = 24) and non-neoplastic polyps (N = 7) using streptavidin-biotin immunohistochemistry and a monoclonal antibody (Serotec: MCA-571) to the EGFR protein. The carcinomas were classified as well differentiated (N = 2), moderately differentiated (N = 16) and poorly differentiated (N = 6). Tissues from metastatic tumor deposits in lymph nodes (N = 5) were also studied. Overexpression of EGFR was present, in the form of strong cytoplasmic immunostaining, in the majority of the SCC cases (n = 20; 83%) and in all of the metastatic tumor deposits. In contrast, although some of the vocal cord polyps showed weak (n = 2) to moderate (n = 5) immunoreactivity, none had evidence of strong EGFR immunoreactivity. The differences in EGFR immunoreactivity were significant between primary laryngeal SCC and vocal cord polyps (p = 0.0001; chi 2 test), and between metastatic laryngeal SCC and vocal cord polyps (p = 0.0001; chi 2 test). Laryngeal carcinoma cases which showed EGFR overexpression had a lower median survival period compared to those without overexpression In conclusion, a different extent of EGFR expression is demonstrated in laryngeal squamous cell carcinomas and non-neoplastic vocal cord polyps using an immunohistochemical method. Some trends in the prognostic value of EGFR immunoreactivity in laryngeal carcinomas appear to emerge in this study.

TGF-alpha immunoreactivity in laryngeal carcinoma: lack of prognostic value and correlation to EGF-receptor expression.

Transforming growth factor alpha (TGF-alpha) is a polypeptide that is structurally similar to epidermal growth factor (EGF) that binds to the epidermal growth factor receptor (EGFR) and has been implicated in the development of several types of human tumours. The expression of TGF-alpha is examined in laryngeal squamous cell carcinoma (SCC) (n = 24) and non-neoplastic polyps (n = 7) using streptavidin-biotin immunohistochemistry and a monoclonal antibody to the TGF-alpha protein. These cases had been previously characterized for EGFR immunoreactivity. The carcinomas were classified as well differentiated (n = 2), moderately differentiated (n = 16) and poorly differentiated (n = 6). Tissues from metastatic tumour deposits in lymph nodes (n = 5) were also studied. TGF-alpha overexpression was defined as intense immunoreactivity in more than two-thirds of tumour cells immunostained for TGF-alpha and was present in the majority of the SCC cases (n = 15; 63%) and metastatic tumour deposits (n = 4; 80%). In contrast, although some of the vocal cord polyps showed weak (n = 2) to moderate (n = 5) immunostaining, none had evidence of strong TGF-alpha immunoreactivity. The differences in TGF-alpha immunoreactivity were significant between primary laryngeal SCC and vocal cord polyps (P = 0.013; chi 2 test with continuity correction), and between metastatic laryngeal SCC and vocal cord polyps (P = 0.023; chi 2 test with continuity correction). There was no significant difference in TGF-alpha expression between the different grades of carcinomas (P = 0.92, chi 2 test) or between non-metastatic and metastatic carcinomas (P = 0.82; chi 2 test with continuity correction). No significant correlation was found between TGF-alpha expression and patient survival or tumour recurrence (r = 0.077, r2 = 0.006, P = 0.75; simple regression analysis), or between TGF-alpha expression and EGFR immunoreactivity (r = 0.325, r2 = 0.106, P = 0.0851). In conclusion, increased TGF-alpha immunoreactivity is present in most cases of laryngeal SCC with no specific relationship to tumour grade, suggesting that it may be important in the development of laryngeal carcinomas but not in its progression. No significant correlation was found between TGF-alpha and EGFR expression in laryngeal tumours and TGF-alpha immunoreactivity is of no prognostic value.

Nm23-H1 protein immunoreactivity in laryngeal carcinoma.

The nm23-H1 gene encodes a 17-kilodalton cytoplasmic and nuclear protein that has recently been shown to be reduced in a number of human carcinomas including breast, colorectal, lung, gallbladder, and biliary tract carcinomas. This study examines the immunohistochemical staining characteristics of the nm23-H1 protein in human laryngeal carcinomas and nonneoplastic laryngeal polyps, and attempts to determine if there is any relationship between reduction of nm23-H1 protein immunoreactivity and prognosis of patients with laryngeal carcinoma. Routine streptavidin-biotin immunohistochemistry with a polyclonal antibody was employed to study the expression of the nm23-H1 protein in laryngeal squamous cell carcinoma (SCC) (N = 22) and nonneoplastic polyps (N = 8). The carcinomas were classified as well differentiated (N = 2), moderately differentiated (N =15), and poorly differentiated (N = 5). Tissues from metastatic tumor deposits in lymph nodes (N = 5) were also studied. A semiquantitative immunostaining index was derived from the intensity and extent of staining of the cells. All laryngeal polyps showed intense immunostaining for the nm23-H1 gene product in the squamous epithelium. However, reduced immunoreactivity was found in nearly half of the SCC cases (N = 10; 46%), with the least staining intensity found in tumor metastases in lymph nodes (N = 4; 80%), and were associated with a shorter median survival of 14.3 months. In contrast, tumors that demonstrated moderate to strong nm23-H1 protein immunostaining were associated with a longer median survival period of 20.4 months. There is reduced expression of the nm23-H1 gene in human laryngeal SCC compared with nonneoplastic laryngeal polyps. Reduction in the intensity and extent of nm23-H1 protein immunostaining appears to correspond to reduced duration of patients survival.

Nm23‐H1 protein immunoreactivity in laryngeal carcinoma

BACKGROUND The nm23-H1 gene encodes a 17-kilodalton cytoplasmic and nuclear protein that has recently been shown to be reduced in a number of human carcinomas including breast, colorectal, lung, gallbladder, and biliary tract carcinomas. This study examines the immunohistochemical staining characteristics of the nm23-H1 protein in human laryngeal carcinomas and nonneoplastic laryngeal polyps, and attempts to determine if there is any relationship between reduction of nm23-H1 protein immunoreactivity and prognosis of patients with laryngeal carcinoma. METHODS Routine streptavidin-biotin immunohistochemistry with a polyclonal antibody was employed to study the expression of the nm23-H1 protein in laryngeal squamous cell carcinoma (SCC) (N = 22) and nonneoplastic polyps (N = 8). The carcinomas were classified as well differentiated (N = 2), moderately differentiated (N = 15), and poorly differentiated (N = 5). Tissues from metastatic tumor deposits in lymph nodes (N = 5) were also studied. A semiquantitative immunostaining index was derived from the intensity and extent of staining of the cells. RESULTS All laryngeal polyps showed intense immunostaining for the nm23-H1 gene product in the squamous epithelium. However, reduced immunoreactivity was found in nearly half of the SCC cases (N = 10; 46%), with the least staining intensity found in tumor metastases in lymph nodes (N = 4; 80%), and were associated with a shorter median survival of 14.3 months. In contrast, tumors that demonstrated moderate to strong nm23-H1 protein immunostaining were associated with a longer median survival period of 20.4 months. CONCLUSIONS There is reduced expression of the nm23-H1 gene in human laryngeal SCC compared with nonneoplastic laryngeal polyps. Reduction in the intensity and extent of nm23-H1 protein immunostaining appears to correspond to reduced duration of patient survival. Cancer 1996;77:2246-50.

Improved control of primary vaginal tumours by combined external-beam and interstitial radiotherapy

In 20 years we have seen only 78 cases of primary vaginal cancer. 61 patients had squamous carcinoma, three had adenocarcinoma, 10 had clear-cell carcinoma, four of which may have been metastatic from carcinoma of the kidney, and four had malignant melanoma. The actuarial 5-year survival of patients with squamous cancer was: Stage I, 68%; Stage II, 34%; Stage III, 29% and Stage IV, 14%. Patients treated by combined external and intracavitary or interstitial radiotherapy had increased local control and superior survival to those treated by interstitial methods alone. The improved tumour control offered by combination treatment may be due to the elimination of small tumour deposits in lymph nodes within the treated volume and the sterilisation of carcinoma in situ in the vagina some distance from obvious tumour.

Morphometrical Assessment of Mean Nuclear Area in Breast Cancer in Comparison with that of Lymph Node Metastases

Morphometrical measurements of nuclear area and form factors are carried out by means of a semiautomated image analyzer on 90 cases of ductal breast cancers and on lymph node tumor deposits. The value of the mean nuclear area in lymph node metastases is significantly higher than in primary tumors regardless of the size of the tumor. Since the value of mean nuclear area is also significantly higher in primary tumors with lymph node involvement than in those without lymph node involvement it is possible to assume that primary tumors with large-nucleus areas are more liable to invade lymph nodes. No significant differences are noted as far as the form factors are concerned.