ABSTRACT
Despite major advances in early detection and prognosis, chemotherapy resistance is a major hurdle in the battle against breast cancer. Identifying predictive markers and understanding the mechanisms are key steps to overcoming chemoresistance. Methylation-controlled J protein (MCJ, also known as DNAJC15) is a negative regulator of mitochondrial respiration and has been associated with chemotherapeutic drug sensitivity in cancer cell lines. Here we show, in a retrospective study of a large cohort of breast cancer patients, that low MCJ expression in breast tumors predicts high risk of relapse in patients treated with chemotherapy; however, MCJ expression does not correlate with response to endocrine therapy. In a prospective study in breast cancer patients undergoing neoadjuvant therapy, low MCJ expression also correlates with poor clinical response to chemotherapy and decreased disease-free survival. Using MCJ-deficient mice, we demonstrate that lack of MCJ is sufficient to induce mammary tumor chemoresistance in vivo. Thus, loss of expression of this endogenous mitochondrial modulator in breast cancer promotes the development of chemoresistance.
ABSTRACT
AIM: To evaluate whether axillary ultrasound in combination with a biopsy (AUS +/- Bx) can predict the involvement of the non-sentinel lymph nodes (NSLN). METHODS: A review of all operable breast cancer patients who underwent AUS +/- Bx at our tertiary care center from January 2010 to April 2011 was performed. All patients underwent AUS as part of their pre-operative evaluation. If the AUS was suspicious, a fine-needle aspiration or core-needle biopsy was performed. RESULTS: Of 88 patients included in our final analysis, 20 (23%) had positive AUS + Bx and underwent axillary lymph node dissection (ALND) at time of definitive surgery. In all, 68 of the 88 patients (77.3%) had negative AUS +/- Bx and underwent sentinel lymph node (SLN) Bx at the time of definitive surgery. If the SLN Bx was negative, no further axillary surgery was performed and the NSLN were assumed to be negative. If the SLN Bx was positive, ALND was performed. Of the 68 patients, 62 (91%) had a negative NSLN. Patients with positive AUS + Bx carry a relative risk of 2.02 (P < 0.00002) of having positive NSLN. CONCLUSION: In operable breast cancer patients, a negative AUS+/- Bx may be a predictor of non-involvement of the NSLN.
Subject(s)
Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Lymph Nodes/diagnostic imaging , Axilla/pathology , Biopsy, Fine-Needle/methods , Breast Neoplasms/surgery , Female , Humans , Lymph Nodes/pathology , Lymphatic Metastasis , Middle Aged , Sentinel Lymph Node Biopsy , UltrasonographyABSTRACT
BACKGROUND: Ovarian metastases from cervical cancers are uncommon. In most cases, the primary site of cervix is known before the occurrence of metastasis. We report a case of cervical adenocarcinoma presenting primarily as advanced ovarian cancer with the primary site totally silent. CASE REPORT: A 47-year old multiparous patient presented to her local hospital with vague abdominal pain for 2 months. Initial investigations with abdominal ultrasound and computerized tomography scan suggested right ovarian dermoid cyst. Her CA125 was 12 micro/ml (0-35). Right salpingo-oophorectomy was performed with the histologic diagnosis of dermoid cyst. Follow-up after 5 months showed a higher level of serum CA 125 (1,594 micro/ml) and a negative cervical smear. Exploratory laparotomy was done with the intent to progress to total abdominal hysterectomy, left salpingo-oophorectomy and omentectomy with staging. Surprisingly, the histologic features of the specimen obtained at laparotomy were consistent with a moderately differentiated cervical adenocarcinoma with metastases to corpus uterus, ovaries, left fallopian tube, omentum and pleural cavity. The final stage was stage IV cervical cancer. Following this, the patient was referred to medical oncologist for chemotherapy. CONCLUSION: Cervical carcinoma should be suspected in any patient presented with bilateral ovarian tumors and positive ascitic fluid cytology. Negative cervical smears do not exclude the possibility of primary cervical carcinoma.
