Three-dimensional histology vs. serial section histology in the treatment of primary basal cell carcinoma: a randomized, prospective, blinded study of 569 tumours.

BACKGROUND: For basal cell carcinoma (BCC), only few controlled data have been published so far, which directly compare micrographically controlled surgery with conventional serial section histology. In addition to Mohs surgery, which uses cryostat sections, also three-dimensional histology (3D-histology), based on paraffin sections, is available to ensure complete control of the margins and basic sections. OBJECTIVES: To investigate the rate of local recurrence (LR) as well as the number of required re-excisions for basal cell carcinomas with serial section histology vs. 3D-histology. METHODS: We compared serial sections histology with 3D-histology in a prospective, randomized, controlled blinded trial and analysed 569 BCC of all subtypes up to 30 mm diameter, 287 BCC in the 3D group and 282 BCC in the serial section group. Excisions were performed with adapted primary resection margin according to location and size of the tumour. Surgeons were blinded at the time of surgery as they did not know which histological method will be used. Both methods used paraffin sections. RESULTS: Both groups did not differ regarding patients age, tumour location, tumour diameter, tumour subtypes or primary resection margins. In the serial section group, re-excisions were required in 21%; 24 tumours (8.4%) recurred after a median of 2.2 years. In the 3D-histology group, re-excisions were required in 39%; 10 tumours recurred (3.5%) after a median of 2.8 years. The recurrence rates differed significantly between both groups. Mean follow-up was 4.5 years. CONCLUSIONS: 3D-histology is a useful technique to detect tumour outgrowths at the excision margins, but required a high rate of re-excisions. 3D-histology was associated with a significantly lower LR rate than serial section histology.

Sentinel node biopsy and cytokeratin staining for the accurate staging of 478 breast cancer patients.

Sentinel lymph node (SLN) mapping is an effective and accurate method of sampling the axillary nodal basin for metastatic disease. The SLN is the first node to receive afferent lymphatic drainage from the primary tumor. Lymphatic mapping and SLN biopsy have allowed pathologists to perform a more detailed examination of the SLN(s) and, therefore, provide more accurate staging of the regional lymphatic basin. Recently, more sensitive assays have been developed to increase the detection rate of micrometastatic to the axillary lymph nodes. Cytokeratin (CK) immunohistochemical (IHC) staining of the SLN detects micrometastatic disease, which is frequently missed on routine hematoxylin and eosin (H&E) histology. Therefore, lymphatic mapping combined with CK IHC staining of the SLN provides more accurate staging of the regional lymph nodes in patients with breast cancer. At Moffitt Cancer Center, 478 patients with newly diagnosed breast cancer underwent intraoperative lymphatic mapping using a combination of vital blue dye and technetium-labeled sulfur colloid. The excised SLNs were examined grossly, by intraoperative imprint cytology, by standard H&E histology, and by IHC stains for CK. SLNs that were only CK positive were confirmed malignant by sectioning the block, staining with H&E and finding cells with malignant cytology. Lymphatic mapping and CK IHC staining of the SLNs was successfully performed in 478 newly diagnosed breast cancer patients. Twenty-eight patients had unsuccessful lymphatic mapping for an overall failure rate of 5.5 per cent. A total of 134 (28%) patients had positive nodes (N1) detected. Ninety-three of these patients had both H&E and CK-positive lymph nodes, and an additional 41 patients had only CK-positive SLN(s). A total of 385 patients had H&E-negative SLNs, but only 344 patients had negative SLN(s) defined as both H&E and CK negative. Therefore, 41 (10.6%) of the 385 H&E-negative patients were upstaged, because of the detection of malignant cells by cytokeratin IHC staining of the SLN. Microstaging of SLNs with CK has shifted 10.6 per cent of our patient population from stage I to stage II disease. Undetected micrometastatic disease to the regional lymph nodes may account for the significant proportion of stage I breast cancer treatment failures. Furthermore, the ability to accurately stage the axilla by using lymphatic mapping techniques, SLN biopsy, and more sensitive assays may help identify a subgroup of truly node-negative patients with invasive breast cancer who can avoid the morbidity associated with a complete axillary dissection or systemic chemotherapy. Finally, those patients found to have micrometastatic disease to the regional lymph nodes can be treated appropriately in a more selective fashion.

Significance of Fas and retinoblastoma protein expression during the progression of Barrett's metaplasia to adenocarcinoma.

BACKGROUND: Barrett's esophagus (BE) is a premalignant lesion characterized by replacement of normal squamous epithelium with columnar epithelium. This lesion can progress to dysplasia and adenocarcinoma. Recently, the Fas receptor and retinoblastoma (Rb) protein have been described as important mediators of apoptosis and tumor suppression, respectively. This study was undertaken to examine their expression during the progression of metaplasia to adenocarcinoma in BE. METHODS: In a review of 56 adenocarcinomas arising in BE, the specimen blocks were examined using the immunohistochemical avidin-biotin-peroxidase complex technique. For each specimen, areas of normal epithelium were compared with areas of metaplasia, dysplasia, or carcinoma (when present). Monoclonal mouse anti-human antibodies were used to identify Rb protein (Rb-Ab5, 1/50 dilution; Oncogene Science) and the 40-50-kDa cell membrane Fas protein (APO-1/Fas, 1/5 dilution; DAKO Corp.). RESULTS: Loss of Rb staining was observed as the metaplasia progressed to dysplasia and carcinoma, indicating accumulation of unstainable aberrant protein. Conversely, Fas protein staining was undetectable or weak in normal or metaplastic epithelium, increasing in the areas of high-grade dysplasia and carcinoma. These differences were statistically significant (P < .001). CONCLUSIONS: The accumulation of abnormal Rb protein during the progression of Barrett's metaplasia to carcinoma leads to unsuppressed tumor growth. Fas overexpression may represent a cellular attempt to balance the uncontrolled tumor proliferation by promoting apoptosis.

Microstaging of breast cancer patients using cytokeratin staining of the sentinel lymph node.

BACKGROUND: Sentinel lymph node (SLN) mapping is an effective and accurate method of axillary nodal evaluation for metastatic disease. Cytokeratin (CK) immunohistochemical (IHC) staining of the SLN has found micrometastatic disease previously undetected by routine hematoxylin and eosin (H&E) stains. The purpose of this study is to determine the number of patients who were upstaged or microstaged, i.e., detected to have micrometastatic disease only by combined lymphatic mapping with CK IHC. METHODS: Two hundred and ten patients with newly diagnosed breast cancer underwent intraoperative lymphatic mapping using a combination of vital blue dye and technetium-labeled sulfur colloid. The excised sentinel lymph nodes were examined grossly, by imprint cytology, by standard H&E histology, and by IHC stains for CK. SLNs that were only CK positive were confirmed to be malignant by histologic examination. RESULTS: CK IHC staining was performed on 381 SLNs in 210 breast cancer patients. Forty-seven of 210 patients (22.4%) had positive nodes. Thirty of these 47 patients (63.8%) had both H&E- and CK-positive SLNs, and an additional 17 of the 47 positive patients (36.2%) had only CK-positive SLNs. Seventeen of the 180 patients (9.4%) who were negative on H&E staining were upstaged by CK IHC staining of malignant cells in the SLN. Comparison of tumor size with the total number of node-positive patients demonstrated that 16 of 30 node-positive T0 and T1 patients (53.5%) and 22 of 39 nodes (56.4%) were upstaged by CK IHC staining. T2 and T3 patients were less frequently upstaged by cytokeratin analysis of lymph nodes. Only one of 17 node-positive patients (5.9%) and seven of 34 nodes (20.6%) in patients with T2 and T3 tumors were upstaged. CONCLUSION: CK IHC staining of SLNs shifted 9.4% of patients from stage I to stage II. There was a significant upstaging influence noted in patients with tumor sizes under 2 cm. This microstaging shift or upstaging may account for the significant proportion of stage I breast cancer treatment failures. Microstaging of the SLNs using more sensitive assays may help identify a subgroup of patients with invasive breast cancer who would benefit from systemic adjuvant treatment, while sparing a disease-free subset of patients the additional risks of toxic adjuvant chemotherapy.

Antitumor agents from bohemic acid complex, III. The isolation of marcellomycin, musettamycin, rudolphomycin, mimimycin, collinemycin, alcindoromycin, and bohemamine.

Six anthracycline antitumor agents, marcellomycin, musettamycin, rudolphomycin, alcindoromycin, collinemycin, and mimimycin, have now been isolated from bohemic acid complex. This has been achieved by classical column chromatography with Sephadex LH-20 and ammonia-neutralized silica and by analytical and prepatative hplc techniques with normal phase systems containing aqueous ammonia.

Synthesis and antitumor properties of 7-deoxy-7-[(cis- and trans-3-aminocyclohexane)thio]carminomycinone.

The synthesis of analogues of carminomycin in which the daunosamine group has been replaced by (cis- and trans-3-aminocyclohexane)thio moieties is described. The new compounds were found to exhibit none of the antitumor or antibiotic activity associated with carminomycin.