HPV-negative carcinoma of the uterine cervix: a distinct type of cervical cancer with poor prognosis.

OBJECTIVE: Using highly sensitive polymerase chain reaction (PCR) techniques, we reanalysed all cervical carcinomas (CCs) found to be human papillomavirus (HPV)-negative by Hybrid Capture 2 (HC2) to determine the prevalence of true HPV-negativity. We also evaluated the characteristics of the patients with tumours with confirmed HPV-negativity. DESIGN: Observational study. SETTING: Barcelona, Spain. POPULATION: A cohort of 136 women with CC (32 adenocarcinomas, 104 squamous cell carcinomas) who had pre-treatment HC2 testing. METHODS: All negative cases were reanalysed and genotyped for HPV using three PCR assays (SPF10, GP5+/6+ and E7-specific assay). MAIN OUTCOME MEASURES: Percentage of confirmed HPV-negative and HPV-positive tumours. Clinicopathological features and disease-free survival (DFS) and overall survival (OS) of both groups. RESULTS: Fourteen of 136 women (10.2%) were negative for HPV by HC2. After reanalysis by PCR-based techniques only 8/136 (5.8%) tumours were confirmed as HPV-negative, whereas in six cases different HPVs were identified [HPV-11, -16 (two tumours), -18, -45, and -68]. Confirmed HPV-negativity was more frequent in adenocarcinomas than in squamous cell carcinomas (5/32, 15.6% versus 3/104, 2.9%, respectively; P = 0.017). Patients with CCs with confirmed HPV-negativity had significantly worse DFS than women with HPV-positive tumours [51.9 months (95% CI 12.2-91.7 months) versus 109.9 months (95% CI 98.2-121.5 months); P = 0.010]. In the multivariate analysis HPV-negativity and International Federation of Gynecology and Obstetrics (FIGO) staging were associated with increased risk of progression and mortality. CONCLUSIONS: An HC2-negative result is an uncommon finding in women with CC, but in almost half of these cases HPVs are identified by more sensitive techniques. CCs with confirmed HPV-negativity are more frequently adenocarcinomas, and seem to be associated with worse DFS.

Use of SPECT/CT for improved sentinel lymph node localization in endometrial cancer.

OBJECTIVE: To assess the usefulness of adding SPECT/CT to planar images for pre-surgical sentinel lymph node (SLN) identification in endometrial cancer (EC), a technique that could have an important clinical impact on the staging, treatment, and prognosis of EC patients. METHODS: We compared the planar and SPECT/CT lymphoscintigraphic images of 44 patients with high-risk EC who underwent sentinel lymph node procedure (SLN) using an injection technique recently developed at our center known as TUMIR (Transvaginal Ultrasound Myometrial Injection of Radiotracer). 148 MBq (4 mCi) of 99mTc-nanocolloid were injected, guided by transvaginal ultrasound imaging. Planar and SPECT/CT images were performed in all 44 patients. RESULTS: SLNs were seen on planar images in 32 cases (73%) and in 34 cases (77%) using SPECT/CT. A total of 88 SLNs were depicted by planar lymphoscintigraphy while SPECT/CT visualized a total of 110 SLNs. SPECT/CT changed the assessment of the SLNs visualized in planar lymphoscintigraphy in 26 cases, either by modifying the number and/or the location of the SLNs detected. External iliac chain was the most frequent location of SLN detection (71%) in the 34 cases. Fifteen of these patients (44%) showed para-aortic SLNs. One case had exclusive para-aortic drainage (3%) that was only visualized by SPECT/CT. In another case, SPECT/CT was able to localize the only pelvic metastatic lymph node not visualized by planar images. CONCLUSIONS: SPECT/CT combined with planar imaging improves preoperative SLN detection and provides valuable anatomic information that enhances the presurgical stage of the SLN technique in endometrial cancer.

Intraoperative post-conisation human papillomavirus testing for early detection of treatment failure in patients with cervical intraepithelial neoplasia: a pilot study.

OBJECTIVE: To evaluate the feasibility and utility of intraoperative post-conisation human papillomavirus (IOP-HPV) testing and cytology to detect treatment failure in patients with cervical intraepithelial neoplasia grades 2-3 (CIN2-3). DESIGN: Prospective observational pilot study. SETTING: Barcelona, Spain. POPULATION: A cohort of 132 women treated for CIN2-3 by loop electrosurgical conisation. METHODS: An endocervical sample was obtained intraoperatively with a cytobrush from the cervix remaining after the conisation. The material was kept in PreservCyt medium and processed for Hybrid Capture 2 and cytology. Patients were followed-up for 24 months. The performance of IOP-HPV testing and IOP cytology was compared with conventional indicators of recurrence (cone margin, endocervical curettage, and HPV testing and cytology at 6 months). MAIN OUTCOME MEASURE: Treatment failure (i.e. recurrent CIN2-3 during follow-up). RESULTS: Treatment failure was identified in 12 women (9.1%). IOP-HPV testing for sensitivity, specificity, and positive and negative predictive values for treatment failure were 91.7, 78.3, 62.2, and 96.0%, respectively, which are similar to the figures for conventional HPV testing at 6 months (91.7, 76.0, 64.0, and 95.1%, respectively), and are better than the values of other conventional predictive factors (cone margin, endocervical curettage, and cytology intraoperative at 6 months). IOP-HPV was strongly associated with treatment failure in the multivariate analysis (OR 15.40, 95% CI 1.58-150.42). CONCLUSION: IOP-HPV testing is feasible, and accurately predicts treatment failure in patients with CIN2-3. This new approach may allow an early identification of patients with treatment failure, thereby facilitating the scheduling of an attenuated follow-up for negative patients who are at very low risk of persistent disease.

Vaginal fertility-sparing surgery and laparoscopic sentinel lymph node detection in early cervical cancer. Retrospective study with 15 years of follow-up.

OBJECTIVE: The aim of this study was to evaluate the oncological outcomes of vaginal fertility-sparing surgery plus laparoscopic sentinel lymph node biopsy in patients with early cervical cancer over a 15-years period. PATIENTS AND METHODS: From March 2005 to April 2018, 38 patients diagnosed with early stage cervical cancer underwent vaginal fertility-sparing surgery at the Hospital Clínic, Barcelona, Spain. Patients with FIGO stage IA1 with lymphovascular space invasion and stage IA2 underwent simple trachelectomy and patients with stage IB1 underwent radical vaginal trachelectomy. All cases underwent laparoscopic sentinel lymph node biopsy. In the first 19 cases, laparoscopic bilateral pelvic lymphadenectomy was completed immediately after sentinel lymph node biopsy. Clinical and oncological follow-up data were collected. RESULTS: The median age at diagnosis was 33.5 years (range 22-44). Simple trachelectomy was performed in seven cases (18.4%) and vaginal radical trachelectomy in 31 (81.6%). Nineteen patients were exclusively treated with laparoscopic sentinel lymph node biopsy and 19 with sentinel lymph node biopsy plus laparoscopic bilateral pelvic lymphadenectomy. There were no significant differences between the two lymph node assessment groups regarding histology and tumour size. The median follow-up was 73 months (range 1-160 months). There were 4 recurrences (3 patients with IB1 and 1 with IA2). Two occurred in the sentinel lymph node biopsy group and 2 in the sentinel lymph node biopsy plus laparoscopic bilateral pelvic lymphadenectomy group. All the recurrences were diagnosed in patients with adenocarcinoma and in 3 patients without lymphovascular space invasion. CONCLUSION: Vaginal fertility-sparing surgery combined with laparoscopic sentinel lymph node biopsy seems to be a safe oncological procedure in selected patients with early stage cervical cancer. Further studies are needed to clarify the role of sentinel lymph node biopsy in fertility- sparing surgery in cervical cancer. Adenocarcinoma histology seems to be an important risk factor for recurrence.

[Sentinel node in gynaecological cancers. Our experience]. / Ganglio centinela en cánceres ginecológicos. Nuestra experiencia.

UNLABELLED: Although sentinel lymph node (SLN) identification is widespread used in melanoma and breast cancer some concerns exist in other malignancies, such gynaecologic cancers, and this staging method has not been adopted in many centers due to lack or large validation studies. AIM: To evaluate the applicability and results of SLN technique in gynaecological malignancies referred to our institution. METHOD: We studied 155 patients with different malignancies (70 vulvar, 50 cervical and 35 endometrial cancers). The day before surgery a lymphoscintigraphy was performed by injecting 111 MBq of (99m)Tc-nanocolloid in several ways depending on the type of cancer studied. Intraoperative detection of the SLN was always performed by using a hand-held gammaprobe and, in 100 cases with the aid of blue dye injection (70 vulvar and 30 in cervical cancer) few minutes before surgical intervention. Pathological study of SLN was performed in all cases. Lymphadenectomy was done in all cervix and endometrial cancer patients and in the first 35 vulvar cancer patients. RESULTS: Pre-surgical lymphoscintigraphy demonstrated one, at least, SLN in 97% of vulvar cancer patients, 92% in the cervical malignancy and 64% in the endometrial cancer patients. During surgery, SLN was harvested in 97%, 90% and 62% of patients, respectively. The pathological study showed metastases in 24.2%, 8.8 and 4.5% of patients with vulvar, cervical and endometrial cancer, respectively. The false negative percentage was 5.5% in vulvar cancer patients, with 2 cases in the endometrial cancer and without any case in the cervical cancer patients. CONCLUSION: Lymphoscintigraphy is a relatively simple and useful technique to identify the SLN in this kind of tumours. However, in endometrial cancer more effort has to be made to reach a suitable result. Sentinel lymph node biopsy seems to be a reliable technique in vulvar and cervical malignancies.

Laparoscopic ovarian transposition in patients with early cervical cancer.

The aim of this study was to evaluate the feasibility, efficacy, and morbidity of laparoscopic ovarian transposition on the preservation of hormonal function in patients younger than 45 years operated for early cervical cancer. According to risk factors on pathologic evaluation of the specimen, some of them will receive postoperative pelvic radiotherapy. This subset of patients could benefit from taking the ovaries away from the irradiation field in an effort to preserve their functionality. This prospective study included 28 FIGO stage IB1 cervical cancer patients, 45 years old or younger, maintaining menstrual cycles, who were considered suitable for conservation of the ovaries. The ovarian transposition was performed by laparoscopy as a part of the same celio-Schauta operation. Twelve patients underwent adjuvant pelvic radiotherapy. No intraoperative or postoperative morbidity related to the ovarian transposition was observed, and the procedure only entailed a minimum delay of the operative time. There were no cases of ovarian metastasis. At a mean follow-up of 44 months, 63.6% of patients receiving radiotherapy and 93% of those who nonirradiated maintained normal ovarian function. Two patients developed benign ovarian cysts, requiring oophorectomy, but no other long-term adverse effects of the transposition were identified. To the best of our knowledge, this is the largest series of the laparoscopic procedure reported to date in this setting. According to our results, laparoscopic ovarian transposition is a safe and effective procedure for the preservation of ovarian function in young patients with early cervical cancer undergoing adjuvant radiotherapy after surgery.

Role of magnetic resonance imaging and cause of pitfalls in detecting myometrial invasion and cervical involvement in endometrial cancer.

OBJECTIVE: To determine the diagnostic accuracy of magnetic resonance imaging (MRI) in detecting myometrial invasion and cervical involvement in endometrial cancer. STUDY DESIGN: Seventy two consecutive patients with endometrial carcinoma underwent preoperative MRI. We compared the MRI results with the final histopathological findings. We classify myometrial invasion as <50 or>or=50% and cervical involvement as positive or negative. Standard statistical calculations were used. RESULTS: The sensitivity, specificity, and accuracy of MRI for the detection of myometrial invasion>or=50% were 71, 86, and 58%, respectively. Positive and negative predictive values are 77 and 83%, respectively. The sensitivity, specificity, and accuracy of MRI for the detection of cervical invasion were 41, 97, and 46%, respectively. Positive and negative predictive values are 71 and 89%, respectively. The possible causes of misdiagnosis included a tumor isointense with the myometrium, polypoid tumor, myometrial thinning, exceedingly irregular myometrium, presence of adenomiosis, and presence of leiomyomas. CONCLUSION: MRI assists in planning the surgical treatment of endometrial cancer with an acceptable accuracy and a good specificity, although sensitivity is suboptimal.

18F-FDG PET/CT and sentinel lymph node biopsy in the staging of patients with cervical and endometrial cancer. Role of dual-time-point imaging.

OBJECTIVE: Definitive staging for cervical (CC) and endometrial cancer (EC) takes place once surgery is performed. The aim of this study was to evaluate the role of PET/CT in detecting lymphatic metastasis in patients with CC and EC using dual-time-point imaging (DPI), taking the histopathological results of sentinel lymph node (SLN) and lymphadenectomy as the reference. MATERIAL AND METHODS: A prospective study was conducted on 17 patients with early CC, and 13 patients with high-risk EC. The patients had a pre-operative PET/CT, MRI, SLN detection, and lymphadenectomy, when indicated. PET/CT findings were compared with histopathological results. RESULTS: In the pathology study, 4 patients with CC and 4 patients with EC had lymphatic metastasis. PET/CT showed hypermetabolic nodes in 1 patient with CC, and 5 with EC. Four of these had metastasis, one detected in the SLN biopsy. Four patients who had negative PET/CT had micrometastasis in the SLN biopsy, 1 patient with additional lymph nodes involvement. The overall patient-based sensitivity, specificity, positive and negative predictive values, and accuracy of PET/CT to detect lymphatic metastasis was 20.0%, 100.0%, 100.0%, 87.9%, and 88.2%, respectively, in CC, and 57.1%, 88.9%, 66.7%, 84.2% and 80.0%, respectively, in EC. DPI showed higher retention index in malignant than in inflammatory nodes, although no statistically significant differences were found. CONCLUSIONS: PET/CT has low sensitivity in lymph node staging of CC and EC, owing to the lack of detection of micrometastasis. Thus, PET/CT cannot replace SLN biopsy. Although no statistically significant differences were found, DPI may help to differentiate between inflammatory and malignant nodes.

[Ovarian and para-aortic recurrence from cervix cancer detected by PET/CT]. / Recurrencia ovárica y paraaórtica de un carcinoma de cuello uterino detectada mediante PET/TC.

We present the case of a 34-year-old woman diagnosed of an adenosquamous carcinoma of the uterine cervix, stage IIB of the FIGO classification (International Federation of Gynecology and Obstetrics), treated with quimiotherapy, radiotheraphy and brachytheraphy with posterior hysterectomy. A recurrence of the disease was suspected due to the progressive rise of CEA levels. A PET/CT revealed abnormal foci in both ovaries, that had been transposed to avoid lesions due to radiation, and in a left para-aortic adenopathy. The diagnosis of recurrence in these sites was confirmed by biopsy. PET with FDG (F18-fluorodeoxyglucose) is useful in the staging of primary tumour and in the detection of recurrence in uterine cervical carcinoma, with better sensitivity and specificity than CT and MRI. PET/CT improves anatomic resolution and helps to resolve the origin of unclear foci like in the case presented in which ovaries were not in their normal situation due to transposition.

Vaginal-cuff control and toxicity results of a daily HDR brachytherapy schedule in endometrial cancer patients.

PURPOSE: To analyze the vaginal-cuff local control (VCC) and toxicity in postoperative endometrial carcinoma patients (EC) underwent high-dose-rate brachytherapy (HDR-BT) administered daily. MATERIALS AND METHODS: 154 consecutive patients received postoperative HDR-BT for EC from January 2007 to September 2011. FIGO-staging I-IIIC2 patients were divided into two groups according to risk classification: Group 1 (94/154) included high-risk or advanced disease patients and Group 2 (60/154) included intermediate-risk EC patients. Group 1 underwent external beam irradiation (EBI) plus HDR-BT (2 fractions of 5 Gy) and Group 2 underwent HDR-BT alone (4 fractions of 5 Gy). Toxicity evaluation was done with RTOG scores for bladder and rectum, and the objective criteria of LENT-SOMA for vagina. RESULTS: With a median follow-up of 46.7 months (36.6-61 months) only two patients developed vaginal-cuff recurrence in Group 1 (2.1 %) and none in group 2 (0 %). Early toxicity in Group 1 appeared 5.3 % in rectum, 7.5 % in bladder (G1-G2) and 2.1 % in vagina (G1); late toxicity was present in 7.3 % in rectum (all G1-G2 but 1 G3) and in 27.7 % in vagina (all G1-G2 but one G4). In Group 2, 6.7 % developed acute G1-G2 bladder and 6.6 % acute vaginal (G1-G2) toxicity. No late rectal or bladder toxicity was observed; 21.7 % of G1-G2 presented late problems in vagina. CONCLUSIONS: The present HDR-BT schedule of 2 fractions of 5 Gy after EBI and 4 fractions of 5 Gy administered daily showed excellent results in terms of VCC and toxicity.

Mesonephric adenocarcinoma of the uterine corpus: CD10 expression as evidence of mesonephric differentiation.

Mesonephric (wolffian) neoplasms of the female genital tract are infrequent and found in sites where embryonic remnants of wolffian origin are usually detected, such as the uterine cervix, broad ligament, mesosalpinx, and ovary. Their diagnosis is difficult because of the absence of specific immunohistochemical markers for mesonephric derivatives. We present the first report of adenocarcinoma of mesonephric type arising as a purely myometrial mass without endometrial or cervical involvement in the uterine corpus of a 33-year-old woman. The tumor showed a combination of patterns, with retiform areas, ductal foci, and small tubules with eosinophilic secretion, which merged with solid sheets of cells with a sarcomatoid appearance. Immunohistochemically, neoplastic cells were diffusely positive for cytokeratin 7, epithelial membrane antigen, and CD15 and focally positive for BerEP4 and vimentin. A hitherto unreported feature was the positivity for CD10 in neoplastic cells, which was also present in a large number of control tissues obtained from male mesonephric derivatives and female mesonephric remnants and tumors. Furthermore, CD10 was negative in controls from müllerian epithelia of the female genital tract and in their corresponding tumors. Therefore, the expression of CD10 by mesonephric remnants may be useful in establishing the diagnosis of tumors with mesonephric differentiation.

Carcinoembryonic antigen in tissue and serum from breast cancer patients relationship with steroid receptors and clinical applications in the prognosis and early diagnosis of relapse.

From July 1982 to August 1994, CEA levels were determined in 298 mammary tissue samples (30 benign, 242 primary breast cancer and 26 metastatic breast cancer). CEA serum levels were also evaluated in 30 patients with benign diseases, 153 patients with primary breast cancer and 26 patients with metastases. CEA tissue levels in both pellet and cytosol were significantly higher in samples from cancerous than from non malignant tissues (p < 0.0001), and higher in the pellet than in the cytosol (p < 0.0001). CEA in the pellet and cytosol were related to steroid receptors, with the highest levels being observed in ER+/PR+ tumors (p < 0.001). They were, however, not related to other pathological parameters such as tumor size or nodes. There was a correlation between CEA pellet and CEA serum in both patients with primary or metastatic tumors, with significantly higher CEA serum levels in patients with CEA pellet positivity than in those with CEA pellet negativity. CEA serum levels were a prognostic factor (DFS and OS) in the whole group as well as in node-positive and node-negative breast cancer patients. This prognostic value was only found in patients with CEA pellet positivity. In the follow-up of 143 NED patients, abnormal CEA serum levels rose prior to the diagnosis of relapse in 73% (29/40) of CEA pellet+ patients with distant recurrences but in only 9% (2/22) of CEA pellet- cases (p < 0.0001). In summary, CEA evaluation in tissue improves the CEA clinical application, selecting those patients whose serum CEA will be useful in the prognosis and early diagnosis of recurrence.

Prospective evaluation of CEA and CA 15.3 in patients with locoregional breast cancer.

The tumor markers, CEA and CA 15.3, were prospectively studied in the sera of 1057 untreated patients with locoregional breast cancer diagnosed from 1983 to 2001. Abnormal CEA and CA 15.3 serum levels were found in 13% and 18.8% of the patients, respectively. One tumor marker or another was abnormal in 22.8% of the patients. Both tumor markers were correlated with tumor size and nodal involvement, with significantly higher concentrations in patients with larger tumors or in patients with nodal involvement. CEA was also related to the histological type and CA 15.3 with the histological grade. Univariate prognostic evaluation showed that tumor size, nodal involvement, histological grade, steroid receptors, adjuvant treatment, CEA, CA 15.3 and treatment before surgery were prognostic factors in both disease-free survival (DFS) and overall survival (OS). Similar results were obtained in node-positive patients, with the same factors being prognostic, excluding adjuvant treatment and CA 15.3, in both DFS and OS. Multivariate analysis showed that tumor size, nodal involvement, histological grade, ER and CEA were independent prognostic factors in both DFS and OS in the whole group as well as in node-positive patients. In contrast, tumor size was the only useful parameter in the prognosis of node-negative patients. CA 15.3 was useful for prognosis (OS) in node-negative patients. In summary, tumor markers are useful tools in the prognostic evaluation of patients with breast cancer.

Prospective evaluation of tumor markers (c-erbB-2 oncoprotein, CEA and CA 15.3) in patients with locoregional breast cancer.

Tumor markers were prospectively (CEA and CA 15.3) or retrospectively (c-erbB-2) studied in the sera of 503 untreated patients with breast cancer diagnosed from 1988 to 2001. Abnormal c-erbB-2 levels (> 15 U/ml) were found in 7%, CEA in 12% and CA 15.3 in 13% of the 503 patients. C-erbB-2 serum levels were only related to c-erbB-2 in tissue, with significantly higher concentrations in patients with positivity in tissue. All the tumor markers (c-erbB-2 only in patients with positivity in tissue) were correlated with tumor size, TNM and nodal involvement. CEA was also related to menopausal status, c-erbB-2 overexpression in tissue and ER. Univariate analysis (mean follow-up 8 years) showed that CEA and CA 15.3 were prognostic factors with significantly shorter disease-free survival (DFS) and overall survival (OS) in patients with pretreatment tumor marker positivity. Multivariate analysis in DFS and in OS showed that nodal involvement CEA and ER but not tumor size, menopausal status, histological grade, histology, CA 15.3, c-erbB-2, PgR, adjuvant treatment, p53 (345 patients) or c-erbB-2 in tissue are independent prognostic factors. In summary, tumor markers are a useful, inexpensive and reproducible tool for prognosis in breast cancer.

C-erbB-2, CEA and CA 15.3 serum levels in the early diagnosis of recurrence of breast cancer patients.

UNLABELLED: C-erbB-2, CEA and CA 15.3 serial serum determinations were performed in 250 patients (follow-up: 1-4 years, mean 2.5 years) with primary breast cancer and no evidence of residual disease (NED) after radical treatment (radical mastectomy or simple mastectomy and radiotherapy). Ninety-five patients developed metastases during follow-up. RESULTS: Abnormal c-erbB-2, CEA and CA 15.3 serum levels (> 20 U/ml, > 10 ng/ml or > 60 U/ml, respectively) prior to diagnosis were found in 28.4%, 31.6% and 46.3% of the 95 patients with recurrence, with a lead time of 4.2 +/- 2.4, 5.0 +/- 2.5 and 4.6 +/- 2.7 months, respectively. One of the tumor markers was the first sign of recurrence in 69.5% of the patients. Tumor marker specificity was 100% with levels lower than the cut-point in all 155 patients without recurrence. Tumor marker sensitivity was clearly related to the site of recurrence, with the lowest sensitivity found in locoregional relapse and the highest in patients with liver or bone metastases. C-erbB-2 sensitivity in early diagnosis was significantly higher in patients with c-erbB-2 overexpression in tissue (10/12, 83.3%) than in those without overexpression (1/34, 2.9%) (p = 0.0001). Likewise, higher levels of both, c-erbB-2 and CA 15.3 at diagnosis of recurrence, higher sensitivity in early diagnosis of relapse and a higher lead time were found in PgR+ patients (CA 15.3) or in PgR- patients (C-erbB-2) (p < 0.015). In conclusion, tumor markers are useful tools for the early diagnosis of metastases, being the first sign of recurrence in 69.5% of patients with relapse (76.3% in patients with metastases).

C-erbB-2 oncoprotein in the sera and tissue of patients with breast cancer. Utility in prognosis.

C-erbB-2 serum levels were studied in the sera of 50 healthy subjects, 56 patients with benign breast diseases and 412 patients with breast cancer. Using 15 U/ml as the cut-off, no healthy subjects, patients with benign disease and only 2.4% of patients with no-evidence of disease had serum levels higher than this cut-off point. Abnormal c-erbB-2 levels were found in 9.2% of the patients with locoregional breast carcinoma and in 45.4% of those with advanced disease. C-erbB-2 serum levels in patients with locoregional breast cancer were not related to tumor size or nodal involvement. By contrast, significantly higher c-erbB-2 serum levels were found in ER- or PgR- tumors than in those ER+ or PgR+ tumors, in both locoregional or metastatic tumors. The correlation between serum and tissue levels of C-erbB-2 was studied in the tumors of 161 patients. Significantly higher c-erbB-2 serum levels were found in patients with overexpression in tissue by immunohistochemistry, in both locoregional and advanced disease (p = 0.0001). In patients with C-erbB-2 overexpression in tissue, c-erbB-2 serum levels were related to tumor size and nodes, with higher values in tumors greater than 5 cm or in those with more than 3 nodes involved. When the prognostic value of this oncoprotein was evaluated, patients with abnormally high presurgical c-erbB-2 had a worse prognosis than those patients with normal values, in both node-negative and node-positive patients. Serum concentrations in patients with advanced disease, were related to the site of recurrence with significantly higher values in patients with metastases (mainly in those with liver metastases) than in those with locoregional recurrence. In summary, c-erbB-2 serum level seem to be a useful tumor marker in the prognosis of patients with breast cancer.

Sentinel lymph node biopsy in breast cancer patients: subdermal versus peritumoural radiocolloid injection.

BACKGROUND AND AIMS: Sentinel lymph node (SLN) biopsy has been widely used in the management of melanoma and breast cancer. The aims of this study were (1) to compare the results obtained with the two main injection techniques, the peritumoural and subdermal; and (2) to determine the reliability of SLN to predict the regional lymph node status. METHOD: We prospectively studied 80 women (mean age 56 years) with breast cancer. Thirty-four of them were T1 and the remaining 46 were T2. Patients were divided into two groups. Group A, 36 patients were injected subdermally, surrounding the tumour site. Group B, 44 patients were injected peritumourally guided by ultrasound if non-palpable. Planar images were performed 15 min after the injection and continued until SLN identification. Before surgery, blue dye injection was administered similarly to the radiocolloid. After incision, a hand-held gamma probe was used to reach the SLN. All nodes harvested were analysed by classic pathology techniques. RESULTS: Overall, lymphoscintigraphy allowed the detection of SLN in 75/80 patients (94%). All subdermal lymphoscintigraphies were positive (36/36) compared with 89% of peritumoural (39/44). Blue dye detected SLN in 23/31 patients (74%) after subdermal injection and in 24/34 patients (71%) after peritumoural injection. The sensitivity to localize the SLN with lymphoscintigraphy+blue dye+gamma probe was 92% (33/36) within the subdermal group and 91% (40/44) within the peritumoural group. Overall, five false negative SLN were found. All of these corresponded to T2 tumours with a size greater than 2.5 cm. The negative predictive value and the accuracy were 93% and 94%, respectively, for the subdermal group and 90% and 93% for the peritumoural group. CONCLUSIONS: (1) Our results indicate that both techniques have similar results. However, we suggest that T2 tumours with a size greater than 2.5 cm should be excluded from the SLN technique, in order to improve the accuracy and negative predictive value. (2) Lymphoscintigraphy is essential for visualizing the SLN, and blue dye can be helpful when the gamma probe does not localize the SLN.

Massive metastases from a lobular breast carcinoma from an unknown primary during pregnancy. A case report.

BACKGROUND: Carcinoma of the breast during pregnancy represents 2-5% of all breast cancers. The frequency and histopathologic spectrum of breast cancer are similar in pregnant and nonpregnant women. Infiltrating lobular carcinoma is one of the less understood types of breast cancer, and its metastatic pattern seems to be different from that of infiltrating ductal carcinoma. Breast neoplasms rarely present as cancer from an unknown primary site. CASE: A woman in the third trimester of pregnancy developed carcinoma massively metastatic to the bone marrow and liver from an unknown primary tumor. At 32 weeks' gestation a healthy male was delivered by cesarean section. The patient died 12 hours after delivery. The autopsy revealed an infiltrating lobular carcinoma, 1.5 cm, of the breast. CONCLUSION: Massive metastases from an occult lobular breast carcinoma in a pregnant woman are very rare. Diffuse metastatic spread, which often complicates or delays the diagnosis, is a characteristic pattern of infiltrating lobular carcinoma. Cancer from an unknown primary site during pregnancy is an exceptional finding. If a metastatic adenocarcinoma is diagnosed in a pregnant woman, a breast primary should be strongly suspected.

[Comparative study of the different radiotracer administration route to locate the sentinel node in breast cancer]. / Estudio comparativo de las diferentes vías de administración del radiotrazador para la localización del ganglio centinela en el cáncer de mama.

AIM: To assess the results of Sentinel Lymph Node (SLN) detection in breast cancer patients depending on the radiotracer injection route, especially evaluating which route that makes it possible to identify the highest percentage of SLNs and its detection in the inner mammary chain. METHODS: We prospectively studied 120 breast cancer patients. Three groups of 40 patients each were established depending on the radiotracer injection route. 1) Subdermal or subareolar route: 18 T1 and 22 T2, mean tumor diameter size of 1.76 cm. 2) Peritumoral route: 16 T1 and 24 T2, mean tumor diameter size of 1.86 cm. 3) Intratumoral route: 20 T1 and 20 T2, mean tumor diameter size of 1.61 cm. The day before surgery, a lymphoscintigraphic study was performed in all cases and intraoperative SLN resection was carried out with the aid of a hand-held gamma probe. RESULTS: The SLN was identified in 38/40 cases (95%) of group 1, in 35/40 cases (88%) of group 2 and in 38/40 cases (95%) of group 3. No SLNs in the mammary chain were observed in patients who underwent subdermal/subareolar injection of the radiotracer. On the other hand, SLNs were visualized in this location in 4/35 patients with peritumoral injection (11%) and in 8/38 patients with intratumoral injection (21%). CONCLUSION: The superficial (subdermal, subareolar) injection technique is more suitable when an unnecessary lymphadenectomy has to be prevented in cases without axillary metastases. The deeper injection technique (peritumoral, intratumoral) should be use when, moreover, we seek accurate staging or plan non-systematic mammary chain irradiation.